Acetonitrile, difluoro- → Methyl 2-(difluoromethyl)-4,5-dihydrooxazole-4-carboxylate

To a cooled (0° C.) solution of sodium methoxide (25 wt % solution in methanol; 0.230 mL, 1.032 mmol) and MeOH (20 mL) was added dropwise difluoroacetonitrile (0.690 mL, 10.03 mmol) while maintaining an internal temperature of <1° C. After 20 min DL-serine methyl ester hydrochloride (1.55 g, 9.96 mmol) was added followed by MeOH (20 mL) and the reaction was allowed to warm to rt overnight. Subsequently, the reaction was heated to 55° C. for 5 h. The reaction was cooled to rt and partitioned between DCM/water. The aqueous layer was extracted with DCM (3×) and the combined organic layers were washed with water and dried over MgSO4. The filtrate was concentrated in vacuo to give 1.59 g (89%) of a light-brown oil. MS m/z=180 [M+H]+. Calculated for C6H7F2NO3:179.

1. temperaturewhile maintaining an internal temperature of <1° C
2. temperatureSubsequently, the reaction was heated to 55° C. for 5 h
3. temperatureThe reaction was cooled to rt
4. custompartitioned between DCM/water
5. extractionThe aqueous layer was extracted with DCM (3×)
6. washthe combined organic layers were washed with water
7. dry with materialdried over MgSO4
8. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-55f4bf2e098e4748920a2bc78e5442ee

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085576B2