Acetaminophen → Ncx-701

Temperature

0 °C

Sodium hydride (270 mg of 60% NaH, 6.8 mmol) was added under argon and under magnetic stirring to a solution of 4-acetaminophenol (840 mg, 5.6 mmol) in dry THF (20 ml) kept at 0° C. The reaction mixture was stirred at 0° C. for 40 minutes. A solution of crude 4-(nitrooxy)butanoyl chloride in dry THF (10 ml), was then added dropwise to the reaction mixture kept at 0° C. The reaction temperature was allowed to rise to r.t. and the mixture was stirred for 18 hours. The unreacted 4-acetaminophenol was removed by washing the solution with 2M NaOH solution (75 ml). The resulting mixture was extracted with CH2Cl2 (3×75 ml). The combined organic phases were dried over MgSO4 and concentrated under reduced pressure. Purification of the residue by silica gel column chromathography by using petroleum ether/ethyl acetate=30/70 mixture as eluent provided 300 mg (1.1 mmol, 40% yield on converted paracetamol) of pure 4-(acetylamino)phenyl 4-(nitrooxy)butanoate.

1. customkept at 0° C
2. customkept at 0° C
3. customto rise to r.t.
4. stirringthe mixture was stirred for 18 hours
5. customThe unreacted 4-acetaminophenol was removed
6. washby washing the solution with 2M NaOH solution (75 ml)
7. extractionThe resulting mixture was extracted with CH2Cl2 (3×75 ml)
8. dry with materialThe combined organic phases were dried over MgSO4
9. concentrationconcentrated under reduced pressure
10. customPurification of the residue by silica gel column chromathography

ORD record

ord-bdc9fae4cbc54a8881364397fb3f88d0

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07442826B2