(R)-N-((5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methylene)-2-methylpropane-2-sulfinamide → (R)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)-2-methylpropane-2-sulfinamide

HRID 404836Notes

Reaction equation

HRID 404836 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]=[N:22][S@@:23]([C:25]([CH3:28])([CH3:27])[CH3:26])=[O:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li][C:30]([CH3:33])([CH3:32])[CH3:31]>C1COCC1>[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[C@H:21]([NH:22][S@@:23]([C:25]([CH3:28])([CH3:27])[CH3:26])=[O:24])[C:30]([CH3:33])([CH3:32])[CH3:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 86693888(R)-N-((5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methylene)-2-methylpropane-2-sulfinamideHCID 178418306HCID 178418306, compound

Product 1

HCID 86693889(R)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)-2-methylpropane-2-sulfinamideYield 53.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (R)—N-((5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)methylene)-2-methylpropane-2-sulfinamide (6.5 g, 15.53 mmol) in anhydrous THF (78 mL) was slowly added tBuLi (1.7 M solution in pentane, 27.4 mL, 46.6 mmol) at −78° C. After the reaction mixture was stirred at −78° C. for 3 h, the reaction was quenched with MeOH (10 mL) followed by addition of saturated NH4Cl solution (30 mL). Upon warming up to room temperature, the reaction mixture was stirred for 30 min and then extracted with EtOAc (250 mL). The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by automatic column chromatography to yield enantiomerically enriched (R)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)-2-methylpropane-2-sulfinamide (3.93 g, 53.1%) as a pale yellow solid. Only single diastereomer was formed and isolated. 1H NMR (CDCl3, 400 MHz): δ 7.87 (1H, m), 7.37-7.29 (3H, m), 7.27-7.21 (2H, m), 7.11-6.96 (2H, m), 4.43-4.28 (2H, m), 4.24-4.09 (2H, m), 1.28 (9H, s), 1.00 (9H, s). LC/MS (uplc): MH+ 477.2, 1.44 min.

Workup

  1. customat −78° C
  2. customthe reaction was quenched with MeOH (10 mL)
  3. additionfollowed by addition of saturated NH4Cl solution (30 mL)
  4. temperatureUpon warming up to room temperature
  5. stirringthe reaction mixture was stirred for 30 min
  6. extractionextracted with EtOAc (250 mL)
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by automatic column chromatography

Sources & evidence

ORD record
ord-d91251d63dd14bebad2cd5eaf22d406b
Source dataset
uspto-grants-2014_06
Patent number
US08748626B2

Reaction notes

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