Hydrochloric Acid → 2-Butyl-5-(4-chlorophenyl)-4-hydroxyisothiazol-3(2H)-one 1,1-dioxide

HRID 729255Notes

Reaction equation

HRID 729255 reaction equation
[CH2:1]([NH:5][S:6]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)(=[O:8])=[O:7])[CH2:2][CH2:3][CH3:4].[C:17](OCC)(=[O:21])[C:18]([O-])=[O:19].CC(C)([O-])C.[K+].Cl>C1COCC1>[CH2:1]([N:5]1[C:18](=[O:19])[C:17]([OH:21])=[C:9]([C:10]2[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=2)[S:6]1(=[O:8])=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 18891362N-butyl-1-(4-chlorophenyl)methanesulfonamideHCID 21943339Ethanedioic acid, monoethyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 686623342-Butyl-5-(4-chlorophenyl)-4-hydroxyisothiazol-3(2H)-one 1,1-dioxideYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

The reaction was done in two vials. In each vial: N-butyl-1-(4-chlorophenyl)methanesulfonamide (0.5 g, 1.91 mmol) was dissolved in THF (3 mL). Ethyl oxalate (0.335 g, 2.29 mmol) was added. The mixture was cooled in an ice-bath. Potassium tert-butoxide (0.28 g, 2.48 mmol)) was added under nitrogen atmosphere. The mixture was heated in a microwave reactor at 150° C. for 10 mins. It was then cooled in an ice-bath. HCl (10%, ca.1 mL) was added, pH˜1. The mixtures of the two vials were combined and evaporated to remove THF. It was then extracted with DCM (20 mL). The extract was dried (MgSO4) and evaporated. Column chromatography (ISOLUTE SI, 20 g/70 mL) of the residue, eluting with heptane, then EtOAc:heptane (20:80), gave fraction A (0.9 g, containing ca. 60% of the title compound) and fraction B (0.035 g, the title compound). 1H NMR (400 MHz, THF-d8): δ 7.92 (d, 2H), 7.50 (d, 2H), 3.68 (t, 2H), 1.82-1.76 (m, 2H), 1.49-1.39 (m, 2H), 0.97 (t, 3H). 13C NMR (100 MHz, THF-d8): 159.2, 146.7, 135.4, 129.8, 129.4, 125.6, 117.7, 39.8, 31.2, 20.6, 13.7. Mass Spectrum: M−H+ 314.

Workup

  1. temperatureThe mixture was cooled in an ice-bath
  2. temperatureIt was then cooled in an ice-bath
  3. customevaporated
  4. customto remove THF
  5. extractionIt was then extracted with DCM (20 mL)
  6. dry with materialThe extract was dried (MgSO4)
  7. customevaporated
  8. washColumn chromatography (ISOLUTE SI, 20 g/70 mL) of the residue, eluting with heptane
  9. customEtOAc:heptane (20:80), gave fraction

Sources & evidence

ORD record
ord-c8597d08caeb40b18edf320f38078d70
Source dataset
uspto-grants-2009_09
Patent number
US07582629B2

Reaction notes

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