Ammonium Chloride → Ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate

To a solution of ethyl 2-ethyl-4-oxocyclopentanecarboxylate (12.82 g, 69.6 mmol, 86% ee, predominantly 1S,2R) in MeOH (183 mL) was added sodium borohydride (3.29 g, 87 mmol) portion-wise. The suspension was stirred at ambient temperature for about 16 h. Saturated aqueous NH4Cl (200 mL) was added and the reaction was stirred for about 3 h. The white precipitate that formed was filtered and washed with Et2O (100 mL). The filtrate was poured into Et2O (300 mL). The solid was filtered and washed with Et2O (50 mL). The layers were separated and the aqueous layer was extracted with Et2O (2×150 mL). The combined organic layers were washed with brine (2×150 mL), dried over anhydrous MgSO4, filtered and concd under reduce pressure (keeping bath temperature about 25° C. and vacuum >50 psi) to give a crude product as a thick light yellow oil. The oil was washed with pentane (5×80 mL). The combined pentane layers were dried over anhydrous MgSO4, filtered and concd to give an oil which was purified by silica gel chromatography using 1:1 EtOAc:pentane to give ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate as a scalemic mixture of diastereomers predominantly (1S,2R,4S)-ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate (12.38 g, 96%) as a clear oil; 1H NMR (400 MHz, CDCl3) δ 4.34-4.25 (m, 1H), 4.23-4.09 (m, 2H), 3.43-3.17 (m, 1H), 2.88 (td, J=7.1, 2.2, 1H), 2.40 (dt, J=14.0, 7.8, 1H), 2.09-1.91 (m, 3H), 1.33-1.24 (m, 4H), 0.95 (t, J=7.4, 3H).

1. stirringthe reaction was stirred for about 3 h
2. customThe white precipitate that formed
3. filtrationwas filtered
4. washwashed with Et2O (100 mL)
5. additionThe filtrate was poured into Et2O (300 mL)
6. filtrationThe solid was filtered
7. washwashed with Et2O (50 mL)
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with Et2O (2×150 mL)
10. washThe combined organic layers were washed with brine (2×150 mL)
11. dry with materialdried over anhydrous MgSO4
12. filtrationfiltered
13. custompressure (keeping bath temperature about 25° C. and vacuum >50 psi)
14. customto give a crude product as a thick light yellow oil
15. washThe oil was washed with pentane (5×80 mL)
16. dry with materialThe combined pentane layers were dried over anhydrous MgSO4
17. filtrationfiltered
18. customto give an oil which
19. customwas purified by silica gel chromatography

ORD record

ord-9e9d267ea69b41e6aa07291399498c7d

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2