4-Methylmorpholine → 2-Cyanoethyl 1-isocyanatomethyl-1-Cyclohexane Acetate

Temperature

-20 °C

1.5 mL of N-methyl morpholine (13.62 mmol) and 1.3 mL of ethyl chloroformate (13.03 mmol) was added to a solution of 1-[(2-cyanoethoxycarbonyl)-methyl]-1-cyclohexane acetic acid (5) (11.84 mmol) in 30 mL of anhydrous THF at −20° C. under nitrogen atmosphere. The reaction mixture was stirred at −20° C. for 20 minutes, warmed to −5° C., an aqueous solution of NaN3 (29.61 mmol, in 3.5 mL of H2O) was added and then stirred for 30 minutes at −5° C. to −10° C. Then, THF was removed under reduced pressure and the residue was extracted with CH2Cl2 and dried over Na2SO4. After concentration in vacuo the crude product was dissolved in 20 mL of anhydrous toluene and refluxed for 20 minutes. The mixture was cooled to room temperature and toluene was removed under reduced pressure. The residue was purified on silica gel (15% ethyl acetate in hexane) to afford 1.9 g (64%) of the title compound. 1H NMR (CDCl3): δ 4.29 (2H, t, J=6.0 Hz); 3.42 (2H, s); 2.73 (2H, t, J=6.0 Hz); 2.44 (2H, s); 1.49-1.39 (10H, m).

1. temperaturewarmed to −5° C.
2. stirringstirred for 30 minutes at −5° C. to −10° C
3. customThen, THF was removed under reduced pressure
4. extractionthe residue was extracted with CH2Cl2
5. dry with materialdried over Na2SO4
6. concentrationAfter concentration in vacuo the crude product
7. dissolutionwas dissolved in 20 mL of anhydrous toluene
8. temperaturerefluxed for 20 minutes
9. temperatureThe mixture was cooled to room temperature
10. customtoluene was removed under reduced pressure
11. customThe residue was purified on silica gel (15% ethyl acetate in hexane)

ORD record

ord-7463070def9040d78b183c126eb06654

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07560483B2