tert-Butanol → (1S,2R)-ethyl 2-methyl-4-oxocyclopentanecarboxylate

In a 1 L round-bottomed flask jacketed flask, copper(I) chloride (0.736 g, 7.43 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4.63 g, 7.43 mmol), and sodium tert-butoxide (0.714 g, 7.43 mmol) in toluene (250 mL) were added to give a yellow solution. The mixture was stirred at ambient temperature for about 15 min. after which the solution became brown. The solution was cooled to about 5° C. and polymethylhydrosiloxane (14.86 mL, 223 mmol) was added and the solution was stirred at about 5° C. for about 40 min. The solution was cooled to about −15° C. and a solution of ethyl 2-methyl-4-oxocyclopent-2-enecarboxylate (25.00 g, 149 mmol) and tert-butyl alcohol (61.7 mL, 654 mmol) in toluene (250 mL) was added in one portion. The reaction stirred at −15° C. for 144 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 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-methyl-4-oxocyclopentanecarboxylate (scalemic mixture of diastereomers), predominantly (1S,2R)-ethyl 2-methyl-4-oxocyclopentanecarboxylate (11.2 g, 42% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 4.19 (qd, J=7.1, 0.6, 2H), 3.17 (ddd, J=8.1, 6.8, 5.6, 1H), 2.76-2.56 (m, 2H), 2.67-2.46 (m, 2H), 2.43-2.29 (m, 2H), 2.16 (ddd, J=18.3, 7.8, 1.7, 1H), 1.29 (t, J=7.2, 3H), 1.06 (d, J=7.0, 3H).

1. customIn a 1 L round-bottomed flask jacketed
2. customto give a yellow solution
3. temperatureThe solution was cooled to about 5° C.
4. stirringthe solution was stirred at about 5° C. for about 40 min
5. temperatureThe solution was cooled to about −15° C.
6. stirringThe reaction stirred at −15° C. for 144 h
7. customThe reaction mixture was quenched by the addition of 1:1 ethanol/toluene (350 mL) and Celite® 545 (25 g)
8. stirringThe mixture was stirred
9. temperatureto warm to ambient temperature
10. additionHeptane (350 mL) was added to the residue and solids
11. customwere removed by filtration
12. customthe crude product was purified by silica gel chromatography

ORD record

ord-bd73c26765bc4ca4a1779ff42515d86e

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426411B2