m-Chloroperbenzoic acid → 2-tert-Butyl-4-({3-[(1-oxidopyridin-3-yl)oxy]propyl}amino)-5-phenylisothiazol-3(2H)-one 1,1-dioxide

HRID 2239646Notes

Reaction equation

HRID 2239646 reaction equation
[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:11][CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[C:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:6]1(=[O:29])=[O:28])([CH3:4])([CH3:3])[CH3:2].C1C=C(Cl)C=C(C(OO)=[O:38])C=1>C(Cl)Cl>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:11][CH2:12][CH2:13][CH2:14][O:15][C:16]2[CH:17]=[N+:18]([O-:38])[CH:19]=[CH:20][CH:21]=2)=[C:7]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[S:6]1(=[O:28])=[O:29])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 115317542-tert-Butyl-5-phenyl-4-{[3-(pyridin-3-yloxy)propyl]amino}isothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 116044182-tert-Butyl-4-({3-[(1-oxidopyridin-3-yl)oxy]propyl}amino)-5-phenylisothiazol-3(2H)-one 1,1-dioxideYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-tert-Butyl-5-phenyl-4-{[3-(pyridin-3-yloxy)propyl]amino}isothiazol-3(2H)-one 1,1-dioxide (Example 5) (0.202 g, 0.49 mmol) was dissolved in dry DCM (15 ml) and cooled to 0° C. with an icebath. mCPBA (70%) (0.120 g, 0.53 mmol) was added and the icebath was removed and the reaction mixture was allowed to reach rt. After stirring for 2 h the reaction mixture was extracted with saturated aqueous NaHCO3 solution (20 ml) and brine (20 ml). The organic phase was dried (Na2SO4), filtered and evaporated. The residue was purified by silica gel column chromatography using a 10:90 mixture of heptane and EtOAc and then DCM:MeOH 97:3 as eluant, to give the title compound (0.160 g, 76%). 1H NMR (500 MHz, CDCl3): δ 7.90-7.83 (m, 2H), 7.51-7.37 (m, 5H), 7.16-7.09 (m, 1H), 6.80-6.74 (m, 1H), 5.68-5.57 (m, 1H), 3.85-3.76 (m, 2H), 3.09-3.02 (m, 2H), 1.85-1.76 (m, 2H), 1.70 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 159.8, 157.0, 135.1, 133.0, 131.8, 129.9, 128.9, 128.2, 125.7, 125.2, 113.5, 107.6, 67.0, 61.8, 60.6, 41.7, 32.1, 28.8, 27.8, 22.9; Mass Spectrum: M−H+ 432.

Workup

  1. customthe icebath was removed
  2. customto reach rt
  3. extractionwas extracted with saturated aqueous NaHCO3 solution (20 ml) and brine (20 ml)
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by silica gel column chromatography
  8. additiona 10:90 mixture of heptane and EtOAc

Sources & evidence

ORD record
ord-54868ea6fdb64eda841c9f4481c0f2e6
Source dataset
uspto-grants-2010_05
Patent number
US07723333B2

Reaction notes

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