Acetyl chloride → 1,1-Dimethylethyl N-[[3-(acetylamino)phenyl]methyl]carbamate

To a stirred solution of tert-butyl 3-aminobenzylcarbamate (Hah, Jung-Mi; Martasek, Pavel; Roman, Linda J.; Silverman, Richard B.; J. Med. Chem.; 2003, 46, 1661-1669) (287 mg, 1.29 mmol) in CH2Cl2 (10 mL) at 0° C. was added Et3N (0.27 mL, 2.0 mmol) and acetyl chloride (0.10 mL, 1.4 mmol) and the resulting solution was warmed up to room temperature slowly. After further stirring of 4 h, the reaction was quenched with saturated aqueous NH4Cl. The layers were separated and the aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organic layer was washed with H2O, brine, dried with Na2SO4 and concentrated under reduced pressure. The residue oil was purified by column chromatography (60% EtOAc in hexanes) to provide tert-butyl 3-acetamidobenzylcarbamate (123.1 mg, 36%). N-(3-(aminomethyl)phenyl)acetamide was then generated by removal of the Boc protecting group by treatment with HCl (in methanol or dioxane) or trifluoroacetic acid in dichloromethane.

1. customthe reaction was quenched with saturated aqueous NH4Cl
2. customThe layers were separated
3. extractionthe aqueous layer was extracted with CH2Cl2 (2×20 mL)
4. washThe combined organic layer was washed with H2O, brine
5. dry with materialdried with Na2SO4
6. concentrationconcentrated under reduced pressure
7. customThe residue oil was purified by column chromatography (60% EtOAc in hexanes)

ORD record

ord-96cf9fc786d34e648dbeebb25ca65dc8

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299267B2