Thionyl Chloride → N-[2-chloro-1-[4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-yl]ethyl]-2,6-difluorobenzamide

HRID 1108155Notes

Reaction equation

S(Cl)([Cl:3])=O.[F:5][CH:6]([F:34])[S:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([CH:20]([NH:23][C:24](=[O:33])[C:25]3[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=3[F:32])[CH2:21]O)=[CH:16][CH:15]=2)=[CH:10][CH:9]=1>C1(C)C=CC=CC=1>[Cl:3][CH2:21][CH:20]([NH:23][C:24](=[O:33])[C:25]1[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=1[F:32])[C:17]1[CH:18]=[CH:19][C:14]([C:11]2[CH:12]=[CH:13][C:8]([S:7][CH:6]([F:34])[F:5])=[CH:9][CH:10]=2)=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 45 °C

Procedure

A portion of 0.37 g (3.1 mmol) of thionyl chloride was added to 1.20 g (2.75 mmol) of N-[1-[4'-[(difluoromethyl)thio][1,1-biphenyl]4-yl]-2-hydroxyethyl]-2,6-difluorobenzamide and 10 mL of toluene. The mixture was warmed to 45° C. for 3.25 h. An additional portion of 0.25 g (2.1 mmol) of thionyl chloride was added and the mixture was stirred for an additional 1 h. The mixture was cooled to 25° C. and the solvent removed under reduced pressure gave the product 1.18 g (96% yield) as an off-white solid. Chromatography on silica gel (eluted with ethyl acetate/hexanes, 1:2) afforded an analytical sample; m.p. 146-147° C. IR (Nujol): 3290, 1652, 1625, 1539, 1311, 1234, 1065, 1009, 818 cm31 1. 1H-NMR(CDCl3): δ3.96-4.08 (m, 2H), 5.62-5.68 (m, 1H), 6.65 (d, J=7.3 Hz, 1H), 6.86 (t, J=57 Hz, 1H), 6.95-7.02 (m, 2H), 7.30-7.48 (m, 3H), 7.50-7.67 (m, 6H).

Workup

temperatureThe mixture was cooled to 25° C.
customthe solvent removed under reduced pressure

Sources & evidence

ORD record: ord-61f1391544394c09a7e3e730867bce30
Source dataset: uspto-grants-2000_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06063932

Reaction notes

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