WillD
Expert
- Joined
- Jul 19, 2021
- Messages
- 789
- Reaction score
- 1,090
- Points
- 93
Reaction scheme:
Benzyl {3-[2-(Benzyldimethylammonio)ethyl]-1H-indol-4-yl} Phosphate.
1. Into a round-bottomed flask was equipped with an overhead stirrer, temperature controller, and dropping funnel was added psilocin (10.3 g, 60.2 mmol) and anhyd THF (500 ml).
2. The mixture was stirred for 15 min and the flask was immersed in a solid CO2 /acetone cooling bath at –78 *C.
3. When the internal temperature of the reaction reached –67 *C, a solution of 2.5M BuLi in hexanes (28.9 ml, 72.3 mmol) was added dropwise over a period of a few min and maintained the internal temperature reading below –60*C.
4. After stirring the olive-green colored reaction mixture for 10 min, tetrabenzyl pyrophosphate (35.7 g, 66.2 mmol) was added in one portion and the mixture was stirred well.
5. After 1.5h, the solid CO2 /acetone cooing bath was removed and the temperature was allowed to slowly rise to –25*C over 2 h.
6. Amino bound silica gel (30 g) was added in one portion and the reaction was diluted with EtOAc (600 ml).
7. The dark mixture was filtered through a pad of Celite and washed with EtOAc (400 ml).
8. The filter cake was reslurried for 10 min with EtOAc (400 ml) and again filtered.
9. The combined filtrates were concentrated and transferred into a 500ml single-necked round-bottomed flask.
10. The gray oil was redissolved in DCM (100ml) and heated with a heat gun to boiling for 5 min.
11. The flask was allowed to reach rt and then held at 4*C overnight.
12. The crude grayish-colored zwitterion precipitate 9 was filtered via Büchner funnel, then triturated with DCM (4x100 ml).
13. The zwitterion precipitate 9 was transferred into a 250 ml single-necked round-bottomed flask and thoroughly dried in the vacuum oven at 40 *C overnight to provide a light-purple solid; yield: 19.2 g (63%).
Psilocybin.
1. Into a 2000 ml round-bottomed flask was added benzyl {3-[2-(benzyldimethylammonio)ethyl]-1H-indol-4-yl} phosphate (16.9 g, 35.6 mmol) followed by CH3OH (1200 ml).
2. The mixture was degassed and refilled with N2.
3. 10% Pd/C (1.1 g) was added, and the mixture was degassed and refilled with H2 balloon at 1 atm.
4. The reaction mixture was stirred overnight at rt.
5. The flask was degassed, refilled with N2 and the suspension was filtered through a pad of Celite via Büchner funnel.
6. The filter pad was washed with CH3OH (500 ml) and the purple colored filtrate was concentrated and dried overnight under vacuum to give 10.7 g of crude 1 (106%).
7. The crude solid was suspended in i-PrOH (200 ml) and boiled for 30 min, then filtered hot (50 to 60 *C).
8. The collected solid was washed with acetone to give a pale purple colored solid.
9. The purple solid was then suspended in 25% CH3OH/i-PrOH and boiled for 30 min and filtered hot, washing with 25% CH3OH/i-PrOH to give a light purple solid.
10. Finally, the solid was recrystallized from 30% H2O in acetone and filtered to give light blue needles.
11. Further recrystallization from 30% acetone/water gave colorless needles.
12. A final recrystallization from deionized H2O (~50 ml) gave a white solid, which was dried in an oven at 60 *C for two days to provide as a white solid; yield: 4.9 g (49%).
Benzyl {3-[2-(Benzyldimethylammonio)ethyl]-1H-indol-4-yl} Phosphate.
1. Into a round-bottomed flask was equipped with an overhead stirrer, temperature controller, and dropping funnel was added psilocin (10.3 g, 60.2 mmol) and anhyd THF (500 ml).
2. The mixture was stirred for 15 min and the flask was immersed in a solid CO2 /acetone cooling bath at –78 *C.
3. When the internal temperature of the reaction reached –67 *C, a solution of 2.5M BuLi in hexanes (28.9 ml, 72.3 mmol) was added dropwise over a period of a few min and maintained the internal temperature reading below –60*C.
4. After stirring the olive-green colored reaction mixture for 10 min, tetrabenzyl pyrophosphate (35.7 g, 66.2 mmol) was added in one portion and the mixture was stirred well.
5. After 1.5h, the solid CO2 /acetone cooing bath was removed and the temperature was allowed to slowly rise to –25*C over 2 h.
6. Amino bound silica gel (30 g) was added in one portion and the reaction was diluted with EtOAc (600 ml).
7. The dark mixture was filtered through a pad of Celite and washed with EtOAc (400 ml).
8. The filter cake was reslurried for 10 min with EtOAc (400 ml) and again filtered.
9. The combined filtrates were concentrated and transferred into a 500ml single-necked round-bottomed flask.
10. The gray oil was redissolved in DCM (100ml) and heated with a heat gun to boiling for 5 min.
11. The flask was allowed to reach rt and then held at 4*C overnight.
12. The crude grayish-colored zwitterion precipitate 9 was filtered via Büchner funnel, then triturated with DCM (4x100 ml).
13. The zwitterion precipitate 9 was transferred into a 250 ml single-necked round-bottomed flask and thoroughly dried in the vacuum oven at 40 *C overnight to provide a light-purple solid; yield: 19.2 g (63%).
Psilocybin.
1. Into a 2000 ml round-bottomed flask was added benzyl {3-[2-(benzyldimethylammonio)ethyl]-1H-indol-4-yl} phosphate (16.9 g, 35.6 mmol) followed by CH3OH (1200 ml).
2. The mixture was degassed and refilled with N2.
3. 10% Pd/C (1.1 g) was added, and the mixture was degassed and refilled with H2 balloon at 1 atm.
4. The reaction mixture was stirred overnight at rt.
5. The flask was degassed, refilled with N2 and the suspension was filtered through a pad of Celite via Büchner funnel.
6. The filter pad was washed with CH3OH (500 ml) and the purple colored filtrate was concentrated and dried overnight under vacuum to give 10.7 g of crude 1 (106%).
7. The crude solid was suspended in i-PrOH (200 ml) and boiled for 30 min, then filtered hot (50 to 60 *C).
8. The collected solid was washed with acetone to give a pale purple colored solid.
9. The purple solid was then suspended in 25% CH3OH/i-PrOH and boiled for 30 min and filtered hot, washing with 25% CH3OH/i-PrOH to give a light purple solid.
10. Finally, the solid was recrystallized from 30% H2O in acetone and filtered to give light blue needles.
11. Further recrystallization from 30% acetone/water gave colorless needles.
12. A final recrystallization from deionized H2O (~50 ml) gave a white solid, which was dried in an oven at 60 *C for two days to provide as a white solid; yield: 4.9 g (49%).
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