2-Fluorophenol → 2-tert-Butyl-4-{[3-(2-fluorophenoxy)propyl]amino}-5-phenylisothiazol-3(2H)-one 1,1-dioxide

HRID 2239624Notes

Reaction equation

HRID 2239624 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].CC1C=CC(S(O[CH2:20][CH2:21][CH2:22][NH:23][C:24]2[C:25](=[O:41])[N:26]([C:37]([CH3:40])([CH3:39])[CH3:38])[S:27](=[O:36])(=[O:35])[C:28]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)(=O)=O)=CC=1>>[C:37]([N:26]1[C:25](=[O:41])[C:24]([NH:23][CH2:22][CH2:21][CH2:20][O:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])=[C:28]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[S:27]1(=[O:35])=[O:36])([CH3:38])([CH3:39])[CH3:40]

Participants

3

Reactant 2

HCID 97072-FluorophenolHCID 866258673-[(2-Tert-butyl-1,1-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]propyl 4-methylbenzenesulfonate

Product 1

HCID 114957362-tert-Butyl-4-{[3-(2-fluorophenoxy)propyl]amino}-5-phenylisothiazol-3(2H)-one 1,1-dioxideYield 62%

Procedure

The title compound was prepared as described for Example 12 from 2-fluorophenol and 3-[(2-tert-butyl-1,1-dioxido-3-oxo-5-phenyl-2,3-dihydroisothiazol-4-yl)amino]propyl 4-methylbenzenesulfonate with a reaction time of 15 mins. The reaction mixture was evaporated and the residue was purified by silica gel column chromatography (Horizons Biotage) using 15% EtOAc in petroleum ether 40-60° C. as eluent then dissolved in EtOAc. The product containing fractions were evaporated and the residue was washed with aqueous K2CO3 (2M) and evaporated to give the title compound (0.063 g, 62%). 1H NMR (500 MHz CDCl3): δ 7.54-7.50 (m, 2H), 7.45-7.40 (m, 3H), 7.11-7.03 (m, 2H), 6.94-6.85 (m, 2H), 5.57 (t, 1H), 3.91 (t, 2H), 3.15-3.10 (m, 2H), 1.90-1.82 (m, 2H), 1.74 (s, 9H); 13C NMR (125 MHz CDCl3): δ 159.8, 153.9, 152.0, 146.8, 146.7, 135.3, 131.8, 129.8, 128.8, 125.2, 124.6, 124.5, 121.9, 121.8, 116.6, 116.5, 115.5, 107.4, 67.2, 61.7, 41.7, 29.2, 27.8. Mass Spectrum M+H+ 433.

Workup

  1. customThe title compound was prepared
  2. customThe reaction mixture was evaporated
  3. customthe residue was purified by silica gel column chromatography (Horizons Biotage)
  4. custom15% EtOAc in petroleum ether 40-60° C.
  5. dissolutionthen dissolved in EtOAc
  6. additionThe product containing fractions
  7. customwere evaporated
  8. washthe residue was washed with aqueous K2CO3 (2M)
  9. customevaporated

Sources & evidence

ORD record
ord-2fecfdde74b645da896385c46467a434
Source dataset
uspto-grants-2010_05
Patent number
US07723333B2

Reaction notes

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