tert-Butanol → Cyclopentanecarboxylic acid, 2-ethyl-4-oxo-, ethyl ester

In a 1 L round-bottomed jacketed flask, copper(I) chloride (0.679 g, 6.86 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4.27 g, 6.86 mmol), and sodium tert-butoxide (0.6.59 g, 6.86 mmol) in toluene (250 mL) were added to give a brown solution. The mixture was stirred at ambient temperature for 15 min after which the solution became brown. The solution was cooled to about 5° C. and polymethylhydrosiloxane (18.29 mL, 274 mmol) was added and the reaction mixture was stirred at about 5° C. for about 40 min. The solution was cooled to about −15° C. and a solution of ethyl 2-ethyl-4-oxocyclopent-2-enecarboxylate (25.00 g, 137 mmol) and tert-butyl alcohol (69.9 mL, 741 mmol) in toluene (250 mL) was added in one portion and the reaction stirred at about −15° C. for about 120 h. The reaction mixture was quenched by the addition of 1:1 ethanol/toluene (350 mL) and Celite® 545 (25 g). The mixture was stirred for about 3 h and allowed to warm to ambient temperature. The reaction mixture was concd in vacuo, chasing with heptane. Heptane (350 mL) was added to the residue and solids were removed by filtration. The filtrate was concd in vacuo and the crude product was purified by silica gel chromatography using a gradient of 10 to 50% EtOAc in heptane over 7 column volumes to give ethyl 2-ethyl-4-oxocyclopentanecarboxylate as a scalemic mixture of diastereomers, predominantly (1S,2R)-ethyl 2-ethyl-4-oxocyclopentanecarboxylate (13.68 g, 54%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 4.17 (qd, J=7.1, 1.5, 2H), 3.25-3.18 (m, 1H), 2.55 (m, J=4.7, 3.5, 1.7, 1H), 2.46-2.29 (m, 3H), 2.21 (m, J=11.6, 9.8, 1.3, 1H), 1.53 (m, J=14.8, 7.4, 6.1, 1H), 1.42-1.30 (m, 1H), 1.27 (t, J=7.1, 3H), 0.98 (t, J=7.4, 3H).

1. customto give a brown solution
2. temperatureThe solution was cooled to about 5° C.
3. stirringthe reaction mixture was stirred at about 5° C. for about 40 min
4. temperatureThe solution was cooled to about −15° C.
5. stirringthe reaction stirred at about −15° C. for about 120 h
6. customThe reaction mixture was quenched by the addition of 1:1 ethanol/toluene (350 mL) and Celite® 545 (25 g)
7. stirringThe mixture was stirred for about 3 h
8. temperatureto warm to ambient temperature
9. additionHeptane (350 mL) was added to the residue and solids
10. customwere removed by filtration
11. customthe crude product was purified by silica gel chromatography

ORD record

ord-a029065d8855404ebfc6818c2bb46645

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2