4-(Difluoromethoxy)aniline → 2-Butyl-5-(4-chlorophenyl)-4-{[4-(difluoromethoxy)phenyl]amino}isothiazol-3(2H)-one 1,1-dioxide

HRID 729280Notes

Reaction equation

[CH2:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[S:6]1(=[O:20])=[O:19])[CH2:2][CH2:3][CH3:4].[F:21][CH:22]([F:31])[O:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1>CC#N>[CH2:1]([N:5]1[C:9](=[O:10])[C:8]([NH:28][C:27]2[CH:29]=[CH:30][C:24]([O:23][CH:22]([F:21])[F:31])=[CH:25][CH:26]=2)=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[S:6]1(=[O:20])=[O:19])[CH2:2][CH2:3][CH3:4]

Participants

Conditions

Temperature: 130 °C

Procedure

2-Butyl-4-chloro-5-(4-chlorophenyl)isothiazol-3(2H)-one 1,1-dioxide (0.20 g, 0.60 mmol) and 4-(difluoromethoxy)-aniline (0.190 g, 1.20 mmol) were mixed in MeCN (2.5 mL). The mixture was heated in a microwave reactor at 130° C. for 15 mins, then additional 60 mins and then at 140° C. for 15 mins, then additional 30 mins. The mixture was evaporated and the residue was purified by column chromatography (ISOLUTE SI 20 g/70 mL), eluting with heptane, then DCM:heptane (25:75, then 50:50), to give the title compound (0.122 g, 45%); 1H NMR (400 MHz, CDCl3): δ 7.28 (s, 1H), 7.12 (d, 2H), 7.04 (d, 2H), 6.81 (d, 2H), 6.70 (d, 2H), 6.37 (t, 1H), 3.76 (t, 2H), 1.87-1.80 (m, 2H), 1.50-1.40 (m, 2H), 0.97 (t, 3H); 13C NMR (100 MHz, CDCl3): δ 158.9, 148.0, 135.6, 133.1, 131.3, 130.3, 128.4, 123.7, 123.1, 120.1, 115.5 (t), 110.1, 40.3, 30.1, 20.0, 13.4; Mass Spectrum: M−H+ 455.

Workup

customadditional 30 mins
customThe mixture was evaporated
customthe residue was purified by column chromatography (ISOLUTE SI 20 g/70 mL)
washeluting with heptane

Sources & evidence

ORD record: ord-5b0ab1b7d6014b4ea50ebaa99701ddb0
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582629B2

Reaction notes

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