Chloroacetyl chloride → 3-(2-chloro-acetylamino)-N-cyclopropyl-4-methylbenzamide

HRID 2252857Notes

Reaction equation

Cl.[NH2:2][C:3]1[CH:4]=[C:5]([CH:12]=[CH:13][C:14]=1[CH3:15])[C:6]([NH:8][CH:9]1[CH2:11][CH2:10]1)=[O:7].CN1CCOCC1.[Cl:23][CH2:24][C:25](Cl)=[O:26]>CC(C)=O>[Cl:23][CH2:24][C:25]([NH:2][C:3]1[CH:4]=[C:5]([CH:12]=[CH:13][C:14]=1[CH3:15])[C:6]([NH:8][CH:9]1[CH2:10][CH2:11]1)=[O:7])=[O:26]

Participants

Conditions

Temperature: -20 °C

Procedure

To a suspension of 3-amino-N-cyclopropyl-4-methyl-benzamide hydrochloride (Compound 1D, 22.7 g, 0.1 mol) in acetone (200 mL) was added 4-methyl morpholine (42.4 mL, 0.3 mol). The solution was cooled to −20° C. and chloroacetyl chloride (12 mL, 0.15 mol) was added dropwise. The reaction mixture was stirred at −10° C. for 10 min before being quenched with H2O (200 mL). The precipitate formed was collected by vacuum filtration and dried to provide 3-(2-chloro-acetylamino)-N-cyclopropyl-4-methyl-benzamide (38C) (25.3 g, 95% yield). mp: decomp 150° C.; 1H NMR(500 MHz, DMSO-D6) δ 9.83 (s, 1H), 8.39 (d, J=3.8 Hz, 1H), 7.82 (s, 1H), 7.58 (d, J=6.6 Hz, 1H), 7.28 (d, J=8.3, 1H), 4.32 (s, 2H), 2.82 (m, 1H), 2.22 (s, 3H), 0.66 (m, 2H), 0.56 (m, 2H); 13C NMR (100 MHz, DMSO-D6) δ: 167.2, 165.4, 136.0, 135.8, 132.8, 130.5, 124.8, 124.7, 43.4, 23.4, 18.1, 6.0; Anal. Calcd for C13H15ClN2O2: C, 58.54; H, 5.66; N, 10.50; Cl, 13.29. Found: C, 53.72; H, 5.95; N, 9.65; Cl, 13.52.

Workup

custombefore being quenched with H2O (200 mL)
customThe precipitate formed
filtrationwas collected by vacuum filtration
customdried

Sources & evidence

ORD record: ord-19d9f9fc93874034a247a5747b613845
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07323482B2

Reaction notes

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