tert-Butylsulfinamide, (R)-(+)- → (R)-N-((5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methylene)-2-methylpropane-2-sulfinamide

HRID 404835Notes

Reaction equation

HRID 404835 reaction equation
[CH2:1]([C:8]1[S:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[CH:21]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([S@:27]([NH2:29])=[O:28])([CH3:26])([CH3:25])[CH3:24]>C1COCC1.[Cl-].[Na+].O.CCOC(C)=O>[CH2:1]([C:8]1[S:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[CH:21]=[N:29][S@@:27]([C:23]([CH3:26])([CH3:25])[CH3:24])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 866938875-Benzyl-2-(2,5-difluorophenyl)thiazole-4-carbaldehyde

Product 1

HCID 86693888(R)-N-((5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methylene)-2-methylpropane-2-sulfinamideYield 94.2%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 5-benzyl-2-(2,5-difluorophenyl)thiazole-4-carbaldehyde (5.2 g, 16.49 mmol) in THF (55.0 mL) was added (R)-(+)-t-butylsulfinamide (2.2 g, 18.14 mmol), and Ti(OEt)4 (7.52 mL, 36.3 mmol). The reaction mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with brine (50 mL) and EtOAc (70 mL) followed by addition of Celite®. Then, the mixture was vigorously stirred for 1 h, and filtered. The filtrate was extracted by EtOAc. The organic layers was washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by automatic column chromatography to yield (R)—N-((5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methylene)-2-methylpropane-2-sulfinamide (6.5 g, 94%) as pale yellow solid. 1H NMR (CDCl3, 400 MHz): δ 8.91 (1H, s), 8.04 (1H, m), 7.38-7.22 (5H, m), 7.16-7.05 (2H, m), 4.62 (2H, s), 1.25 (9H, s). LC/MS (uplc): MH+ 419.1, 1.31 min.

Workup

  1. additionfollowed by addition of Celite®
  2. stirringThen, the mixture was vigorously stirred for 1 h
  3. filtrationfiltered
  4. extractionThe filtrate was extracted by EtOAc
  5. washThe organic layers was washed with water and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by automatic column chromatography

Sources & evidence

ORD record
ord-b1fd6f259afa4d28bff9b1986f74060f
Source dataset
uspto-grants-2014_06
Patent number
US08748626B2

Reaction notes

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