Triethylamine → 4-Chloro-N-methoxy-N-methylbenzamide

Temperature

0 °C

A 1-L, three-necked, round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and an addition funnel was charged with N,O-dimethylhydroxylamine hydrochloride (20 g, 0.20 mol) and CH2Cl2 (250 mL). The mixture was cooled to 0° C. and triethylamine (24 g, 0.20 mol) was added, followed by a solution of 4-chlorobenzoyl chloride (35.8 g, 0.2 mol) in CH2Cl2 (100 mL). After the addition was complete, the cooling bath was removed, and the reaction was allowed to warm to rt and was stirred overnight. The reaction mixture was quenched with satd. aq. NH4Cl (200 mL). The mixture was transferred to a separatory funnel, the layers were separated and the aqueous layer was extracted with CH2Cl2 (200 mL). The combined organic layers were washed with aq. NaHCO3, brine, and then dried over anhydrous MgSO4. After filtration, the solvents were evaporated under reduced pressure to afford the benzamide (37 g, 92%) as a colorless oil. IR (film): 2935, 1639, 1593, 1460, 1415, 1212, 1090, 1015, 887, 838, 747, 730 cm−1. 1H NMR (400 MHz, CDCl3): δ7.58 (d, J=8.6 Hz, 2H), 7.32 (d, J=8.6 Hz, 2H), 3.55 (s, 3H), 3.11 (s, 3H). 13C NMR (100 MHz, CDCl3): δ169.2, 137.3, 132.9, 130.5, 128.8, 61.7, 34.1. HRMS (EI): m/z calcd for C9H11ClNO2 [M+H]+, 200.0478; found, 200.0484.

1. additionAfter the addition
2. customthe cooling bath was removed
3. temperatureto warm to rt
4. customThe reaction mixture was quenched with satd
5. customThe mixture was transferred to a separatory funnel
6. customthe layers were separated
7. extractionthe aqueous layer was extracted with CH2Cl2 (200 mL)
8. washThe combined organic layers were washed with aq. NaHCO3, brine
9. dry with materialdried over anhydrous MgSO4
10. filtrationAfter filtration
11. customthe solvents were evaporated under reduced pressure

ORD record

ord-30840878b9f5488a905dae2b4792dd68

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07507756B2