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ARGONAUT TECHNOLOGIES Quest 21 0: User Tutorial R'OH or Et SLEt H PS-DES (150 mg, ArgoCap) A R' (6equiv I R~ 7 mol% RhCI(PPh3)3 NMP (3 mL), 60°C, 3 h 1) 0.4 M HFIpyridine in THF (4 mL) 2) MeOSiMe3 (0.5 mL, 2 equiv. relative to - Figure 1. Synthesis of Resin Bound Ethers to Form the Corresponding Alcohol The objective of the Quest 2 10 Organic Synthesizer Tutorial is to introduce and familiarize new users to the instrument.
Material Source ArgoCaps (PS-DES) Argonaut Comment 150 mg/capsule, Wilkinson's catalyst Chlorotris(triphenylphosphine) rhodium(1) (RhC1(PPhj); 1-(2-methoxybenzoy1)-2 pGolidinemethanol 1-na~hthaleneethanol 2,2-diphenylethanol Epiandrosterone 4-biphenylcarboxaldehyde HFiwridine .- Strem -0.68 mmollg* FW 925.23 1 Aldrich I FW 235.
polycarbonate capsules (ArgoCaps) are placed into the RVs and washed three times with 4 mL of dichloromethane (DCM). The efficient removal of the capsule by organic solvent demonstrates the convenience of using ArgoCaps for solid-phase synthesis. After performing a solvent exchange with anhydrous 1-methyl-2-pyrrolidinone (NMP), PSDES resin is allowed to react with a selection of alcohols and carbonyls (0.3 M in NMP) using R l ~ c l ( P P h as ~ ) catalyst ~ at an elevated temperature.
I AlcohoVCarbonyl AlcohollCarbonyl Amount Structure 1-naphthaleneethanol 2.2-diphenylethanol 1 206 mgl 4 rnL NMP Ph h Ph 238 mgl oH 4 rnL NMP 218 mgl 4 rnL NMP I Table 3. Preparation of Alcohol and Carbonyl Solutions in Anhydrous NMP (0.3 M) B. Instrument Preparation Before proceeding, prepare the appropriate alcohol/carbonyl and catalyst solutions needed for the tutorial.
Drain I Figure 2. Quest 210 Reactor Unit Installation of an Oil Bubbler and Purging the System - This synthesis requires an oil bubbler be installed in the Utility 1 port located at the top of the instrument (Figure 3). Use 118 inch Teflon tubing to connect the oil bubbler to the Quest 21 0. The bubbler outlet should be pointed towards the back of the fume hood and away from the Quest. Fittings are provided with the Quest to interface with an oil bubbler, or any other external accessory.
Figure 3. Location of Manifold Controls and Utility Ports Once the oil bubbler is installed, ensure that it is functioning properly by doing the following: 1 Verify the Upper Manifold Membrane Pressure Switch is "OPEN". 2 Turn the Manifold Control Valves to "UTILITY 1" and "METERED GAS". Drain Gas Utility 1 Metered Gas Utility 2 The metered gas is regulated by the Metered Gas Needle Valve located next to the utility ports on the top of the Reactor Unit (Figure 3).
using the white Teflon Drain Lever provided with the Quest to drain all I0 RVs in parallel. Drain Gas Metered Gas Utility 1 Utility 2 Leaving the Lower Manifold Drain Valves open, turn off the Drain Gas (set the left valve to "CLOSED") and turn on the METERED GAS. Note- Do not turn the Manifold Control Valves to "DRAIN GAS" and "METERED GAS" simultaneously. Drain Gas Metered Gas Utility 1 Utility 2 c.
D. RV Removal & Instrument Cleaning 1. To remove the RVs from Side A (RVs 1-10) use the following protocol. a. Position the rotating lever on the right side of the Reactor Unit so that is sticking out from the right side of the Quest parallel to the bench top. Rotate the lever in towards the front of the Quest 2 10 Reactor Unit.
Figure 5. Using the RV mount as a fulcrum, twist the RV to "break it free" from the Lower Drain Manifold male RV fitting and "twist-up" using the RV holder as a fulcrum (Figure 5) to break the RV free of the clamping ring (Figure 6). Take care not to bump the tube inserts which protrude from the Upper Manifold male RV fittings. Figure 6. The RV is Free from the Lower Drain Manifold male RV fitting.
Figure 7. Remove the RV from the holder With your fingers, remove the RV from the Reactor Unit (Figure 7) Using a sharp pair of scissors, cut the top of the RV off below the crimp from the RV extraction tool. Use the external hand magnet provided in the Quest starter kit to remove the magnet mixers from the RV. Remove the magnets by sliding the magnets out through the top of the RV. Wash the magnetic mixers with an appropriate solvent such as acetone.
RV Installation Slide ten 5 mL RVs between the aluminum heating plate and spring loaded insulators on the Reactor Unit. Press them down over the male Teflon RV fittings on the Lower Drain Manifold. Do not attempt to fully seat the RVs at this time. Place the Reaction Vessel Insertion Tool on top of the RV as shown in Figure 8. Figure 8.
4. Check that the vessels are fully seated over the male Teflon RV fittings of the Lower Drain Manifold. If the vesseIs are seated properly, the tops of the vessels will be horizontally uniform and the frits will be seated just above or on the male Teflon RV fittings of the Lower Drain Manifold (Figure 10). Figure 10. Proper installation of the Quest RVs 11. Coupling Reaction To a bank of ten RV's (e.g., RVs 1-10, Side A), an ArgoCap of PS-DES resin is added.
Figure 11. Quest Controller Unit display Place a single magnet mixer into each RV with the fin facing downward. Use the external hand magnet found in the Quest starter kit to align the magnet mixers with the magnetic agitation bar. Lower the Upper Manifold onto the RVs by doing the following: a. Push in the silver buttons on the blue handles of the Upper Manifold. b. Using the Upper Manifold handles, slowly slide the Upper Manifold onto the tops of the RVs.
T m both Manifold Control Valves to "CLOSED" Drain Gas Solvent Metered Gas Closed Vent Utility 1 @- Closed Utility 2 Unscrew the Solvent Bottle Cap from the 4 L bottle. Wipe off any residual solvent on the Solvent Bottle Pick-Up Line. Dispose of the white polyethylene SolventIReagent Inlet Filter and install a new one on the end of the Solvent Bottle Pick-Up Line. Replace the 4 L solvent bottle in the Safety Container with a 4 L bottle of DCM. Take care not to misplace the Teflon bottle seal.
2. Close the Upper Manifold by first turning the left Manifold Control Valve to "CLOSED", then turn the right Manifold Control Valve to "CLOSED". D. Drain Gas Metered Gas Utility 1 Utility 2 Adjusting the Agitation Bar 1. Ensure that the Agitator Bar is in the UP position (move the agitator up by pushing the Agitation UP button located to the right of the Quest Controller Unit display). 2. Use the 7/64" hex wrench supplied with the Quest to loosen the Agitation Stops.
Press the Right or Left soft keys),'( to select the % Upward parameter (the amount of time the agitation bar remains in the up most position expressed as a percentage of the agitation frequency). Use the PARAMETER SETTING soft keys (?&) to increase or decrease the %Upward parameter to the following: %Upward= 95%. Turn the agitation on by pushing the Agitation ON soft key located to the right of the Quest Controller Unit display.
Raise the handle so the Lower Manifold Drain Valves are closed. Add -4 mL DCM to the RVs by turning the Manifold Control Valves to "SOLVENT" and "VENT". When the delivery is complete, purge the Upper Manifold by slowly turning the left Manifold Control Valve to "DRAIN GAS". Close the Upper Manifold by turning both of the Manifold Control Valves to "CLOSED". Turn the agitation on by pushing the Agitation ON soft key located to the right side of the Quest Controller Unit display.
8. Move the agitator up by pressing the Agitation UP soft key located to the right of the Quest Controller Unit display. 9. Turn the Manifold Control Valves to "DRAIN GAS" and "CLOSED". Drain Gas Utility 1 Metered Gas Utility 2 10. Use the white Teflon Drain Lever to OPEN the Lower Manifold Drain Valves and drain all 10 RVs in parallel to the Waste Tank. Allow the nitrogen to purge the resin for -30 seconds. 11. Raise the Teflon Drain Lever and close the Lower Manifold Drain Valves. 12.
H. Addition of Reagent Under Nitrogen to the Reaction Vessels 1. Adjust the Metered Gas Needle Valve located on the top of the Quest Reactor Unit until you see a steady stream of gas bubbling through the oil bubbler when one of the Luer Plugs is removed from the Upper Manifold. 2. Using a syringe add the alcohol or carbonyl diversity reagent in NMP to each RV. a.
On the Quest Controller Unit press the MODE soft key located below the LCD display until the Agitation menu is displayed. Set parameters as follows: Mix Every 4.0 sec and %Upward= 60%. Turn the agitation on by pushing the Agitation ON soft key located to the right of the Quest Controller Unit display. If solvent is splashing up onto the Upper Manifold, readjust the height of the agitation.
9. The heaters will shut off when the timer runs out and the RVs will begin cooling to ambient temperature. ----------------- A (ON) SET ACT B (OFF) 60.0 20.0 60.9 1 6 - 2 02:59:35 0O:OO:OO Figure 15. Temperature monitor display K. Draining the RVs 1. After the instrument has returned to room temperature (-30 min.), open the Upper Manifold Membrane by following these steps: a. Vent the Upper Manifold by turning the Manifold Control Valves to "CLOSED" and "VENT". b.
h. Install the bottle cap assembly onto the 4L bottle of NMP. Ensure the Teflon bottle seal is placed in the bottleneck and tighten the bottle cap. Turn the black dial on top of the Solvent Bottle Cap towards the tubing marked "Bottle Pressure". Wait a -1 minute for the bottle to pressurize. 2. Fill the RVs with NMP by turning the Manifold Control Valves to "SOLVENT" and "VENT".
111. CleavageIScavenger of the Resin and Product Collection Cleavage solution (0.4 M HFIPyridine in THF, 4 mL) is added to the washed resin using a syringe and the mixture agitated for 2 h at room temperature. HF scavenger (Me;SiOMe, 0.5 mL) is added to each RVs via syringe and the mixture agitated at room temperature for an additional 2 h. The solvent from each RV is collected into 10-preweighed scintillation vials. The resin is then washed twice with THF (3 mL, 5 min. agitation).
Turn the agitation on by pushing the Agitation ON soft key located to the right side of the Quest Controller Unit display. If solvent is splashing up into the Upper Manifold, readjust the height of the agitation. The Mix Speed Needle Valve located on the front of the Quest Controller Unit may also be used to soften or slow the agitation by turning the valve clockwise. Agitate the resin in cleavage solution for 2 hours at room temperature.
bottom of the Lower Manifold. The silver buttons will snap out to verify that the collection tray is locked into position. 5. Ensure that each Teflon collection line is inside its own scintillation vial and that the two vent lines are clear of any vials. 6. Move the agitator up by pushing the Agitation UP soft key located to the right of the Quest Controller Unit display. 7. Vent the Upper Manifold of the Quest to prepare for the controlled draining of the RV contents into the scintillation vials. a.
c. On the Quest Controller Unit press the MODE soft key located below the LCD display until the Agitation menu is displayed. Set the agitation parameters as follows: Mix Every 4.0sec. and %Upward= 60%. 3. Turn the agitator on by pushing the Agitation ON soft key located to the right of the Quest Controller Unit display. If solvent is splashing up onto the Upper Manifold, readjust the height of the agitation.
1V. Cleaning the Quest (Maintenance) and Sample Work UpIAnalysis To ensure the Quest 2 10 is ready for the next synthesis it is recommended to flush the Upper Manifold, all delivery lines, Luer Plugs and the Lower Manifold with a solvent compatible with the synthesis. Dispose of the solvent waste in accordance with local laws and regulations. Flushing the System Place the empty glass waste tank under the Quest Reactor Unit. Move the tray to its upper most position using the waste tray handles.
B. Sample Work Up 1. Using a Savant SpeedVac (Model SS620DDA SpeedVac or equivalent), evaporate the solvent from the 20 mL scintillation vials containing the product. 2. Re-weigh the scintillation vials and calculate the product mass yields using the weights determined earlier. 3. Add 5 mL THF to each scintillation vial, mix to dissolve the products, and analyze by Gas Chromatography for product purity (Table 4).
C. IR and GC Product Analysis Infrared Analysis Infrared spectra were recorded on a Nicolet Impact 41 0 spectrometer equipped with an InspectIR microscope using a random sampling of single beads Figures 16 and 17 are representative spectra of the PS-DES resin and the corresponding resin-bound ether.
ame~r~usue~~o~ Figure 1 6 . PS-DES Infrared S p e c t r a Artisan Technology Group - Quality Instrumentation ... Guaranteed | (888) 88-SOURCE | www.artisantg.
agUey1WSUEJ 1 % F i g u r e 17. PS-DES-OR Infrared S p e c t r a Artisan Technology Group - Quality Instrumentation ... Guaranteed | (888) 88-SOURCE | www.artisantg.
S o r r e d Ey Xrrltiplier Dilution Totals : F i g u r e 18.-Ana2p5is of I-(2-methoxybenzoyl)-2-pyrr~lidinemethanol Artisan Technology Group - Quality Instrumentation ... Guaranteed | (888) 88-SOURCE | www.artisantg.
Artisan Technology Group - Quality Instrumentation ... Guaranteed | (888) 88-SOURCE | www.artisantg.
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Vial- : Fisure 21. Analysis of 99 pia and roster one Artisan Technology Group - Quality Instrumentation ... Guaranteed | (888) 88-SOURCE | www.artisantg.
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Artisan Technology Group is your source for quality new and certified-used/pre-owned equipment • FAST SHIPPING AND DELIVERY • TENS OF THOUSANDS OF IN-STOCK ITEMS • EQUIPMENT DEMOS • HUNDREDS OF MANUFACTURERS SUPPORTED • LEASING/MONTHLY RENTALS • ITAR CERTIFIED SECURE ASSET SOLUTIONS SERVICE CENTER REPAIRS Experienced engineers and technicians on staff at our full-service, in-house repair center WE BUY USED EQUIPMENT Sell your excess, underutilized, and idle used equipment We also offer credit for buy-back