Ethanol → HCID 67490764, compound

Temperature

40 °C

Lithium borohydride (4.96 g, 0.228 mol) was suspended in tetrahydrofuran (500 mL). A solution of (3R)-3-allyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (50.0 g, 0.152 mol) in tetrahydrofuran (100 mL)-ethanol (17.7 mL) was added to the suspension using a dropping funnel over 10 minutes. The mixture was heated to 40° C., stirred for 12 hours, and then heated to reflux for 20 hours. After cooling to 0° C., a saturated ammonium chloride solution (100 mL) was carefully added. After the tetrahydrofuran component was evaporated under reduced pressure, the reaction solution was poured into a mixture of ethyl acetate (100 mL) and a saturated ammonium chloride solution (100 mL), followed by extraction with ethyl acetate (1000 mL, 750 mL). The organic layers were combined and washed with brine (200 mL). After drying over anhydrous sodium sulfate and filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:4) to give 29.9 g (76%) of the title compound as a colorless viscous oil.

1. customover 10 minutes
2. temperatureheated
3. temperatureto reflux for 20 hours
4. temperatureAfter cooling to 0° C.
5. customAfter the tetrahydrofuran component was evaporated under reduced pressure
6. additionthe reaction solution was poured into a mixture of ethyl acetate (100 mL)
7. extractiona saturated ammonium chloride solution (100 mL), followed by extraction with ethyl acetate (1000 mL, 750 mL)
8. washwashed with brine (200 mL)
9. dry with materialAfter drying over anhydrous sodium sulfate and filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:4)

ORD record

ord-bb3904f63acc41a098f7545fe6fccd9c

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2