tert-Butanol → Ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate

A mixture of copper (I) chloride (0.136 g, 1.37 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.854 g, 1.37 mmol), and NaOt-Bu (0.132 g, 1.37 mmol) in toluene (50 mL) was stirred at ambient temperature for about 15 min then cooled to about 5° C. and polymethylhydrosiloxane (12 mL, 55 mmol) was added. The reaction mixture was stirred for about 40 min at about 5° C. then cooled to about −12° C. A solution of ethyl 2-ethyl-4-oxocyclopent-2-enecarboxylate (5.00 g, 27.4 mmol) and t-BuOH (14 mL, 148 mmol) in toluene (50 mL) was added in one portion and the reaction mixture was stirred for about 16 h at about −12° C. The reaction mixture was quenched by the addition of MeOH (50 mL). The solvents were removed under reduced pressure. The residue was dissolved in MeOH (35 mL) and filtered through a pad of Celite®. The filtrate was concd under reduced pressure and the residue was triturated with EtOAc (100 mL) and filtered. The filtrate was concd under reduced pressure and the residue was purified using silica gel chromatography eluting with a gradient of 0-10% EtOAc in heptane to give a scalemic mixture enriched with (1S,2R,4S)-ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate (1.11 g, 22%): 1H NMR (CDCl3) δ 4.30 (m, 1H), 4.24-4.08 (m, 2H), 2.88 (td, J=2.1, 7.1 Hz, 1H), 2.40 (dt, J=7.8, 14.0 Hz, 1H), 2.08-1.91 (m, 3H), 1.52-1.31 (m, 3H), 1.29 (t, J=7.1 Hz, 3H), 0.94 (t, J=7.4 Hz, 3H).

1. temperaturethen cooled to about 5° C.
2. stirringThe reaction mixture was stirred for about 40 min at about 5° C.
3. temperaturethen cooled to about −12° C
4. stirringthe reaction mixture was stirred for about 16 h at about −12° C
5. customThe reaction mixture was quenched by the addition of MeOH (50 mL)
6. customThe solvents were removed under reduced pressure
7. dissolutionThe residue was dissolved in MeOH (35 mL)
8. filtrationfiltered through a pad of Celite®
9. customthe residue was triturated with EtOAc (100 mL)
10. filtrationfiltered
11. customthe residue was purified
12. washeluting with a gradient of 0-10% EtOAc in heptane
13. customto give a scalemic mixture

ORD record

ord-be97392cbdd2407cb45913396fa4bcf2

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2