Methanol → 875467-74-6

Temperature

0 °C

1.9 g of (R (4-chloro-phenyl)-hydroxy-acetonitrile (11 mmol) were dissolved in 18 ml THF under a nitrogen atmosphere and the solution was cooled to 0° C. 58 ml of a 1M borane-THF complex solution in THF were then added dropwise, keeping the temperature between 0-2° C. After completion of the addition the reaction mixture was stirred at RT for additional 45 min and then refluxed for 16 h. The reaction mixture was then cooled down to 0° C. and 13 ml of methanol were added over a period of 35 min keeping the temperature of the mixture between 2 and 5° C. After refluxing the reaction mixture for 1 h it was concentrated, the remaining residue was dissolved in DCM and the mixture was extracted twice with 1N aqueous HCl. The combined aqueous phases are then treated with concentrated NaOH to adjust the pH to 12, and then extracted twice with DCM. The combined organic phases were then washed with water, dried with magnesium sulfate, filtered and concentrated in vacuo leading to a colorless solid which was dissolved in 100 ml diethylether, treated with 4 ml 2.6N HCl in diethyl ether. After 1 h at RT the precipitate was filtered off and dried under high vacuum, leading to 1.24 g white solid (54%). MS (ISP) 172.1 (M+H)+.

1. custombetween 0-2° C
2. additionAfter completion of the addition the reaction mixture
3. temperaturerefluxed for 16 h
4. temperatureThe reaction mixture was then cooled down to 0° C.
5. customthe temperature of the mixture between 2 and 5° C
6. temperatureAfter refluxing the reaction mixture for 1 h it
7. concentrationwas concentrated
8. dissolutionthe remaining residue was dissolved in DCM
9. extractionthe mixture was extracted twice with 1N aqueous HCl
10. additionThe combined aqueous phases are then treated with concentrated NaOH
11. extractionextracted twice with DCM
12. washThe combined organic phases were then washed with water
13. dry with materialdried with magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. dissolutionwas dissolved in 100 ml diethylether
17. additiontreated with 4 ml 2.6N HCl in diethyl ether
18. filtrationAfter 1 h at RT the precipitate was filtered off
19. customdried under high vacuum

ORD record

ord-fb352e715d134cc7893658674c184f0c

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07678818B2