4-Methylmorpholine → trans-N-cyanomethyl-2-hydroxymethyl-cyclohexanecarboxamide

Temperature

-78 °C

(1R,2R)-2-{[(Cyanomethyl)amino]carbonyl}cyclohexanecarboxylic acid (97 mg, 0.46 mmol) in a 25 mL round bottom flask was fitted with a rubber septum and the flask was flushed with nitrogen. After adding tetrahydrofuran (1 mL), the reaction mixture was cooled to −78° C. and 4-methylmorpholine (51 μL, 0.47 mmol) and isobutyl chloroformate (51 μL, 0.46 mmol) were added. After 5 min, the reaction mixture was warmed quickly to 0° C. for 30 minutes. After recooling to −78° C., sodium borohydride (45 mg, 1.2 mmol) and methanol (1 mL) were added. After 5 min., the reaction mixture was allowed to warm to ambient temperature over 2 h. After quenching with 1 mL saturated aqueous ammonium chloride, the reaction mixture was partitioned between saturated aqueous sodium chloride solution and ethyl acetate. The organic layer was separated, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated. Toluene (5 mL) was added and stirring was carried out overnight. The solution was decanted and the residue was dried to give (1R,2R)-N-(cyanomethyl)-2-(hydroxymethyl)cyclohexanecarboxamide as a colorless powder.

1. customthe flask was flushed with nitrogen
2. additionAfter adding tetrahydrofuran (1 mL)
3. temperaturethe reaction mixture was warmed quickly to 0° C. for 30 minutes
4. customAfter recooling to −78° C.
5. waitAfter 5 min.
6. temperatureto warm to ambient temperature over 2 h
7. customAfter quenching with 1 mL saturated aqueous ammonium chloride
8. customthe reaction mixture was partitioned between saturated aqueous sodium chloride solution and ethyl acetate
9. customThe organic layer was separated
10. washwashed with saturated sodium chloride aqueous solution
11. dry with materialdried over anhydrous sodium sulfate
12. concentrationconcentrated
13. additionToluene (5 mL) was added
14. waitwas carried out overnight
15. customThe solution was decanted
16. customthe residue was dried

ORD record

ord-454f1fecb36e449381cc6243b31eff3c

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07371747B2