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

온도

35 °C

The E/Z mixture of ethyl 2-(7-(benzyloxy)-1,2-dihydrocyclopenta[b]indol-3(4H)-ylidene)acetate (7.5 g, 21.59 mmol) and 10% Pd/C (50% wet; 1.13 g, 10.58 mmol) were taken up in ethyl acetate (60 mL, 613 mmol). The suspension was degassed 3× with N2 and followed with pre-activation of the catalyst with the addition of formic acid (2.48 mL, 64.8 mmol). The mixture was allowed to stir for 1-2 min. Triethylamine (9.03 mL, 64.8 mmol) was charged portion-wise maintaining the temperature<35° C. Upon complete addition of triethylamine, the mixture was stirred for about 5-10 minutes followed with heating to 50° C. The reaction progression was followed by HPLC to monitor the complete consumption of starting material (i.e., E/Z mixture of ethyl 2-(7-(benzyloxy)-1,2-dihydrocyclopenta[b]indol-3(4H)-ylidene)acetate) and the debenzylated intermediate. Approximately after 4 h at 50° C., the solution was cooled to about 20° C., the Pd/C was removed via vacuum filtration and rinsed with ethyl acetate (30 mL). To the filtrate was added water (75 mL) and the biphasic mixture was partitioned. The organics were washed with water (2×60 mL), concentrated under vacuum with a bath temp of 40° C. to a minimum stir volume, chased with ethyl acetate (1×37.5 mL) and further concentrated under vacuum to a minimum stir volume. Ethyl acetate (11 mL) was charged to the crude mixture and the resulting solution was heated to 60° C. Heptanes (34 mL) were charged maintaining the internal temperature at 60° C. The solution was slowly cooled to 10° C. and held for 30 min. The slurry was filtered, the filter cake rinsed with heptanes (2×52.5 mL) and the solids dried in the vacuum oven set to 40° C. to afford the title compound (2.78 g, 74.5% yield) as light beige solids.

1. customThe suspension was degassed 3× with N2
2. stirringthe mixture was stirred for about 5-10 minutes
3. temperaturewith heating to 50° C
4. customthe complete consumption of starting material (i.e., E/Z mixture of ethyl 2-(7-(benzyloxy)-1,2-dihydrocyclopenta[b]indol-3(4H)-ylidene)acetate)
5. waitApproximately after 4 h at 50° C.
6. temperaturethe solution was cooled to about 20° C.
7. customthe Pd/C was removed via vacuum filtration
8. washrinsed with ethyl acetate (30 mL)
9. additionTo the filtrate was added water (75 mL)
10. customthe biphasic mixture was partitioned
11. washThe organics were washed with water (2×60 mL)
12. concentrationconcentrated under vacuum with a bath temp of 40° C. to a minimum stir volume
13. concentrationfurther concentrated under vacuum to a minimum stir volume
14. additionEthyl acetate (11 mL) was charged to the crude mixture
15. temperaturethe resulting solution was heated to 60° C
16. additionHeptanes (34 mL) were charged
17. temperaturemaintaining the internal temperature at 60° C
18. temperatureThe solution was slowly cooled to 10° C.
19. waitheld for 30 min
20. filtrationThe slurry was filtered
21. washthe filter cake rinsed with heptanes (2×52.5 mL)
22. customthe solids dried in the vacuum oven
23. customset to 40° C.

ORD 기록

ord-cd9f3952c2984f858e8e33ed219eb08d

출처 데이터셋

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08853419B2