Formic Acid → Ethyl 2-(7-hydroxy-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate

温度

20 °C

To a 3-neck 250 mL round bottom flask was charged E/Z mixture of ethyl 2-(7-(benzyloxy)-1,2-dihydrocyclopenta[b]indol-3(4H)-ylidene)acetate (15 g, 432 mmol) and purged with N2. 10% Pd/C (50% wet; 2.34 g, 22.02 mmol) was charged and the contents degassed 3× with N2 followed by addition of ethyl acetate (120 mL, 1226 mmol). The solution was degassed 3× with N2 and followed by the pre-activation of the catalyst with the addition of formic acid (4.97 mL, 130 mmol). The mixture was allowed to stir for 1-2 minutes. Triethylamine (18.05 mL, 130 mmol) was charged drop-wise maintaining an internal temperature between about 24° C. to 30° C. The reaction was held at 30° C. for 1 h to allow for reaction completion. The reaction progression was monitored by HPLC. Upon reaction completion, the solution was cooled to 20° C. and the catalyst Pd/C was removed via vacuum filtration and rinsed with 30 mL of ethyl acetate. Water (90 mL) was charged to the filtrate and the biphasic mixture was partitioned. The organics were washed with water (2×90 mL), concentrated under vacuum in bath temp 40° C. to a minimum stir volume, chased with ethyl acetate (1×30 mL) and further concentrated under vacuum to a minimum stir volume. Ethyl acetate (22.5 mL) was charged to the crude and the resulting solution was heated to 60° C. Heptanes (67.5 mL) were charged maintaining the internal temperature at 60° C. whereupon crystallization was initiated. The slurry was cooled to 40° C. and aged for 1 h, further cooled to 5-10° C. and aged for 0.5 h. The slurry was filtered, the filter cake rinsed with heptanes (2×60 mL) and the solids dried in the vacuum oven set to 40° C. to afford the title compound (8.86 g, 79% yield) as light beige solids.

1. additionTo a 3-neck 250 mL round bottom flask was charged
2. custompurged with N2
3. customthe contents degassed 3× with N2
4. customThe solution was degassed 3× with N2
5. temperaturemaintaining an internal temperature between about 24° C. to 30° C
6. waitThe reaction was held at 30° C. for 1 h
7. customto allow for reaction completion
8. customUpon reaction completion
9. customthe catalyst Pd/C was removed via vacuum filtration
10. washrinsed with 30 mL of ethyl acetate
11. additionWater (90 mL) was charged to the filtrate
12. customthe biphasic mixture was partitioned
13. washThe organics were washed with water (2×90 mL)
14. concentrationconcentrated under vacuum in bath temp 40° C. to a minimum stir volume
15. concentrationfurther concentrated under vacuum to a minimum stir volume
16. additionEthyl acetate (22.5 mL) was charged to the crude
17. temperaturethe resulting solution was heated to 60° C
18. additionHeptanes (67.5 mL) were charged
19. temperaturemaintaining the internal temperature at 60° C.
20. customwhereupon crystallization
21. temperatureThe slurry was cooled to 40° C. and aged for 1 h
22. temperaturefurther cooled to 5-10° C. and aged for 0.5 h
23. filtrationThe slurry was filtered
24. washthe filter cake rinsed with heptanes (2×60 mL)
25. customthe solids dried in the vacuum oven
26. customset to 40° C.

ORDレコード

ord-47eaf106e79744bebbc45c6a7778254d

出典データセット

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09447041B2