4-Methylmorpholine → (4-Bromo-2-chlorophenyl)methanol

Temperature

-15 °C

4-Bromo-2-chlorobenzoic acid (14, 92.0 g, 0.39 mol) was dissolved in dry tetrahydrofuran (920 mL) and cooled to −15° C. Isobutyryl choroformate (51.0 mL, 0.39 mol) was added followed by N-methylmorpholine (43.5 mL, 0.39 mol). The resulting mixture was stirred for 10 minutes at −15° C., cooled to −25° C. and the precipitated N-methylmorpholine hydrochloride salt was filtered off. The filtrate was warmed to −5° C. and a solution of sodium borohydride (22.19 g, 0.586 mol) in water (190 mL) was added dropwise to the mixture keeping the temperature below 0° C. After stirring for 1 h at 0° C., the volatiles were evaporated, and the residue was diluted with water (500 mL) and dichloromethane (450 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (150 mL). The combined organic layers were washed with water (150 mL), dried over sodium sulfate and evaporated. The product (86.1 g, 0.39 mol, 99%) was obtained as a white crystalline solid.

1. temperaturecooled to −25° C.
2. filtrationthe precipitated N-methylmorpholine hydrochloride salt was filtered off
3. temperatureThe filtrate was warmed to −5° C.
4. customthe temperature below 0° C
5. stirringAfter stirring for 1 h at 0° C.
6. customthe volatiles were evaporated
7. additionthe residue was diluted with water (500 mL) and dichloromethane (450 mL)
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with dichloromethane (150 mL)
10. washThe combined organic layers were washed with water (150 mL)
11. dry with materialdried over sodium sulfate
12. customevaporated

ORD record

ord-77a4f13cf2ec48ffac0a69b6d9120db5

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372970B2