Triethylamine → cis-hexahydroisobenzofuran-1(3H)-one

Into a 25 mL jacketed vessel cooled to below 0° C. was placed a solution of (1S,2R)-2-(methoxycarbonyl) cyclohexane carboxylic acid (3, 880 mg, 4.72 mmol) and triethylamine 659 μL, 4.72 mmol) in THF (6.6 mL). A solution of ethyl chloroformate (512 μL, 4.72 mmol) in 1.2 mL of THF was added slowly over a few minutes and the resulting mixture was stirred for 30 minutes. The precipitated triethylamine hydrochloride salt was removed by filtration and the filtrate was added drop-wise to a suspension of sodium borohydride in 4.6 mL of water at 12° C. After the addition was complete, the reaction mixture was stirred at 20° C. for a further 3.5 hours. The reaction mixture was then cooled to below 10° C., acidified to pH 4 with 2M HCl solution, and extracted with 2×15 mL of dichloromethane. The combined organic extracts were dried over magnesium sulfate and solvent was removed under reduced pressure, to yield 450 mg of a colorless oil. The material was purified by short path distillation to yield 170 mg of colorless oil with e.e.=98% and [α]D20=−39.3° (c 1, methanol).

1. temperatureInto a 25 mL jacketed vessel cooled to below 0° C.
2. customThe precipitated triethylamine hydrochloride salt was removed by filtration
3. additionthe filtrate was added drop-wise
4. additionto a suspension of sodium borohydride in 4.6 mL of water at 12° C
5. additionAfter the addition
6. stirringthe reaction mixture was stirred at 20° C. for a further 3.5 hours
7. temperatureThe reaction mixture was then cooled to below 10° C.
8. extractionextracted with 2×15 mL of dichloromethane
9. dry with materialThe combined organic extracts were dried over magnesium sulfate and solvent
10. customwas removed under reduced pressure

ORD record

ord-86e1e53c76344a57bd3ffd79d3dd716b

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09080193B2