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

HRID 1108159Notes

Reaction equation

[Cl:1][CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH:18]([F:20])[F:19])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)O.[F:21][C:22]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:23]=1[C:24]#[N:25].S(=O)(=O)(O)[OH:32]>ClCCl>[Cl:1][CH2:2][CH:3]([NH:25][C:24](=[O:32])[C:23]1[C:22]([F:21])=[CH:29][CH:28]=[CH:27][C:26]=1[F:30])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH:18]([F:20])[F:19])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 5 °C

Procedure

A mixture of 2.0 g of α-(chloromethyl)-4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-methanol, 4.0 g of 2,6-difluorobenzonitrile, and 15 mL of dichloromethane was cooled to 5° C. and 0.8 mL of conc. sulfuric acid was added dropwise over 7 min. After 30 min, ice was added, the mixture was diluted with hexanes, and the crude product was filtered and dried to afford 1.0 g of product, m.p. 144-145° C. 1H-NMR (CDCl3): δ4.0 (dq, 2), 5.6 (m, 1H), 6.75 (br d, 1H), 6.85 (t, 1H, J=60 Hz), 7.0 (t, 2H), 7.4 (m, 1H), 7.5 (d, 2H), 7.6 (m, 6H). The filtrate was extracted with ethyl acetate; the extract was washed with water, concentrated, and chromatographed on silica gel to afford an additional 0.5 g of product, corresponding to a total yield of 52%.

Workup

additionice was added
filtrationthe crude product was filtered
customdried

Sources & evidence

ORD record: ord-49c934ab843c4ee99893b14191cce85d
Source dataset: uspto-grants-2000_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06063932

Reaction notes

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