Dimethylformamide → 4-Chloro-2-[4-(difluoromethoxy)benzyl]-5-phenylisothiazol-3(2H)-one 1,1-dioxide

HRID 729262Notes

Reaction equation

HRID 729262 reaction equation
[F:1][CH:2]([F:26])[O:3][C:4]1[CH:25]=[CH:24][C:7]([CH2:8][N:9]2[C:13](=[O:14])[C:12](O)=[C:11]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[S:10]2(=[O:23])=[O:22])=[CH:6][CH:5]=1.CN(C=O)C.C(Cl)(=O)C([Cl:35])=O>C(Cl)Cl>[Cl:35][C:12]1[C:13](=[O:14])[N:9]([CH2:8][C:7]2[CH:24]=[CH:25][C:4]([O:3][CH:2]([F:26])[F:1])=[CH:5][CH:6]=2)[S:10](=[O:23])(=[O:22])[C:11]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 68662198HCID 68662198, compound

Product 1

HCID 686617234-Chloro-2-[4-(difluoromethoxy)benzyl]-5-phenylisothiazol-3(2H)-one 1,1-dioxideYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[4-(Difluoromethoxy)benzyl]-4-hydroxy-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.98 g, ca.60% purity, 1.80 mmol)) was dissolved in DCM (40 mL) and DMF (0.14 mL) was added. Under an atmosphere of nitrogen, oxalyl chloride (0.46 g 3.61 mmol) was dropped in. The mixture was then heated to reflux for 5 h and then evaporated to dryness. Water (20 mL) was added and the reaction mixture was extracted with DCM (20 mL×3). The extracts were combined and washed with water (50 mL×3) and brine (20 mL), dried (MgSO4) and evaporated. The residue was purified by column chromatography (ISOLUTE SI, 20 g/70 mL), eluting with DCM:heptane (30:70), to give the title compound (0.442 g, 62%) as a semi-solid; 1H NMR (400 MHz, CDCl3): δ 7.97 (d, 2H), 7.48-7.58 (m, 5H), 7.11 (d, 2H), 6.51 (t, 1H), 4.86 (s, 2H); 13C NMR (100 MHz, CDCl3): δ 155.8, 151.2, 143.5, 132.5, 130.8, 130.5, 129.4, 128.8, 127.2, 123.2, 119.5, 115.7 (t), 43.1.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureto reflux for 5 h
  3. customevaporated to dryness
  4. additionWater (20 mL) was added
  5. extractionthe reaction mixture was extracted with DCM (20 mL×3)
  6. washwashed with water (50 mL×3) and brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was purified by column chromatography (ISOLUTE SI, 20 g/70 mL)
  10. washeluting with DCM:heptane (30:70)

Sources & evidence

ORD record
ord-d613227ea93c498ebb26b5554b293f84
Source dataset
uspto-grants-2009_09
Patent number
US07582629B2

Reaction notes

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