Sodium Cyanide → (S)-tert-Butyl (1-cyanopropan-2-yl)carbamate

Temperature

35 °C

Sodium cyanide (48.92 g, 0.421 mol) was added to dimethylformamide (DMF) (420 mL) and the mixture was stirred at 35° C. for 30 minutes. Tetrabutylammonium bromide (5.22 g, 0.016 mol) was added and the reaction mixture was stirred for an additional 2 h at 35° C. Methanesulfonic acid 2-(S)-tert-butoxycarbonylamino-propyl ester (82.03 g, 0.324 mol) was added and the reaction mixture was stirred at 35° C. overnight. Add an additional 5.22 g of tetrabutylammonium bromide (0.016 mol) was added and stirred overnight at 35° C. The mixture was then partitioned between 1200 mL water and 1600 mL of ethyl acetate. The resulting organic and aqueous phases were separated and extracted sequentially 2 times with 800 mL of ethyl acetate. The combined extracts were washed 3 times with 500 mL of water and a saturated solution of sodium chloride in water. The organic layer was dried over magnesium sulfate, filtered and concentrated to afford a solid in 84% of (S)-(2-cyano-1-methyl-ethyl)-carbamic acid tert-butyl ester.

1. stirringthe reaction mixture was stirred for an additional 2 h at 35° C
2. stirringthe reaction mixture was stirred at 35° C. overnight
3. additionwas added
4. stirringstirred overnight at 35° C
5. customThe mixture was then partitioned between 1200 mL water and 1600 mL of ethyl acetate
6. customThe resulting organic and aqueous phases were separated
7. extractionextracted sequentially 2 times with 800 mL of ethyl acetate
8. washThe combined extracts were washed 3 times with 500 mL of water
9. dry with materialThe organic layer was dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford a solid in 84% of (S)-(2-cyano-1-methyl-ethyl)-carbamic acid tert-butyl ester

ORD record

ord-16f26f1b88eb42b2827fcd8c33a4c03d

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07211672B2