Chloroacetyl chloride → 2-chloro-N-(2-chloro-6-fluorophenyl)-N-(4-methylphenyl)acetamide

HRID 749263Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=1.[Cl:17][CH2:18][C:19](Cl)=[O:20]>CC(O)C.CCCCCC>[Cl:17][CH2:18][C:19]([N:9]([C:3]1[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])[C:10]1[CH:11]=[CH:12][C:13]([CH3:16])=[CH:14][CH:15]=1)=[O:20]

Participants

Conditions

Temperature: 37.5 °C

Procedure

20.4 g of crude (2′-chloro-6′-fluorophenyl)-(4-methylphenyl)-amine are heated to about 80° C. and treated with 10.75 g of chloroacetylchlonde. The mixture is stirred for 2 hours and diluted with 10 ml of 2-propanol. The solution is cooled to 35-40° C. and seeded. The precipitated suspension is diluted with 30 ml of hexane, cooled to 0-5° C. and stirred for about 1 hour. The crystals are isolated by filtration, washed with a cold solution of 2-propanol/hexane ⅓. After drying, 22.7 g of 2-chloro-N-(2′-chloro-6′-fluorophenyl)-N-(4-methylphenyl)acetamide are obtained. HPLC purity: 99%. Melting point: 79-80° C. 1H-NMR(DMF-d7, 400 MHz, 393K) δ 2.44(s, 3H, CH3); 4.32 (s, 2H, CH2), 7.35[d, J=8.0 Hz, 2H, HC(3) and HC(5)], 7.43[ddd, J=8.0, 2.0 Hz, JH-F=8.0, 1H, HC(5′)], 7.48[d, J=8.0 Hz, 2H, HC(2) and HC(6)], 7.55[d, J=8.0 Hz, 1H, HC(3′)], 7.60[ddd, J=8.0 Hz, JH-F=5.5, 1H, HC(4′)].

Workup

temperaturecooled to 0-5° C.
stirringstirred for about 1 hour
customThe crystals are isolated by filtration
washwashed with a cold solution of 2-propanol/hexane ⅓
customAfter drying

Sources & evidence

ORD record: ord-ee14ba8f00194a2897a0f4a2df3dbdac
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07402603B2

Reaction notes

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