4-Methylmorpholine → trans-N-(cyanomethyl)-2-(hydroxymethyl)-cyclopentanecarboxamide

Temperature

-78 °C

trans-2-{[(Cyanomethyl)amino]carbonyl}cyclopentanecarboxylic acid (860 mg, 4.38 mmol) was placed in a 50 mL round bottom flask. The flask was fitted with a rubber septum and then flushed with nitrogen. Tetrahydrofuran (9 mL) was added and the reaction mixture was cooled to −78° C. 4-Methylmorpholine (0.53 mL, 4.8 mmol) was added, followed by addition of isobutyl chloroformate (0.61 mL, 4.7 mmol). The reaction mixture was warmed to ambient temperature over 1.5 h and then recooled to −78° C. Sodium borohydride (0.28 g, 7.4 mmol) was added and then methanol (3.0 mL). The reaction mixture was stirred at −78° C. for 2 h and then quenched with saturated aqueous ammonium chloride (10 mL). The reaction mixture was warmed to ambient temperature and then poured into 100 mL saturated aqueous sodium chloride solution. The product was extracted into ethyl acetate. The combined organics were dried over anhydrous sodium sulfate and then concentrated on a rotary evaporator. Toluene (5 mL) was added to the residue and the reaction mixture was stirred for 30 min. The solution was removed by decantation and the residue was dried under high vacuum to give trans-N-(cyanomethyl)-2-(hydroxymethyl)-cyclopentanecarboxamide as a colorless solid.

1. customThe flask was fitted with a rubber septum
2. customflushed with nitrogen
3. additionTetrahydrofuran (9 mL) was added
4. temperatureThe reaction mixture was warmed to ambient temperature over 1.5 h
5. customrecooled to −78° C
6. customquenched with saturated aqueous ammonium chloride (10 mL)
7. temperatureThe reaction mixture was warmed to ambient temperature
8. additionpoured into 100 mL saturated aqueous sodium chloride solution
9. extractionThe product was extracted into ethyl acetate
10. dry with materialThe combined organics were dried over anhydrous sodium sulfate
11. concentrationconcentrated on a rotary evaporator
12. additionToluene (5 mL) was added to the residue
13. stirringthe reaction mixture was stirred for 30 min
14. customThe solution was removed by decantation
15. customthe residue was dried under high vacuum

ORD record

ord-1fd10d48685f41aa8011b13d33e38b0e

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07371747B2