Triethylamine → HCID 66645641, compound

Temperature

-40 °C

A cooled (−40° C.) solution of cyclopropylacetic acid (5.13 g, 51.250 mmol) in anhydrous tetrahydrofuran (150 mL) was subsequently treated with triethylamine (21.4 mL, 153.75 mmol) and trimethylacetyl chloride (6.9 mL, 56.375 mmol). After stirring at −40° C. for 1 h, the mixture was treated with (S)-4-benzyl-oxazolidin-2-one (9.99 g, 56.375 mmol) and lithium chloride (2.39 g, 56.375 mmol). The mixture was allowed to slowly warm to room temperature and after stirring at room temperature for 22 h, the reaction was partitioned between dichloromethane and half-saturated ammonium chloride. The aqueous layer was extracted with dichloromethane. The organics were combined, filtered through a phase separator and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 9:1 to afford the title compound (11.63 g, 87%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.19-0.32 (m, 2H), 0.56-0.69 (m, 2H), 1.10-1.24 (m, 1H), 2.76-2.87 (m, 2H), 2.96 (dd, J=16.9, 6.9 Hz, 1H), 3.34 (dd, J=13.2, 3.3 Hz, 1H), 4.15-4.29 (m, 2H), 4.66-4.77 (m, 1H), 7.20-7.40 (m, 5H). LCMS (m/z) 282.1 [M+Na], Tr=2.78 min.

1. temperatureto slowly warm to room temperature
2. stirringafter stirring at room temperature for 22 h
3. customthe reaction was partitioned between dichloromethane and half-saturated ammonium chloride
4. extractionThe aqueous layer was extracted with dichloromethane
5. filtrationfiltered through a phase separator
6. customthe volatiles were removed in vacuo
7. customThe residue was purified by silica gel chromatography
8. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 9:1

ORD record

ord-ed23d9f6b81b4e30abfb4534a712b5bd

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062092B2