3,5-Dimethylisoxazole → (R)-N-(bis(3-(trifluoromethoxy)phenyl)-methylene)-2-methylpropane-2-sulfinamide

HRID 1874160Notes

Reaction equation

HRID 1874160 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[O:4][N:3]=1.[Li]CCCC.[F:13][C:14]([F:42])([F:41])[O:15][C:16]1[CH:17]=[C:18]([C:22]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:40])([F:39])[F:38])[CH:31]=2)=[N:23][S:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH:19]=[CH:20][CH:21]=1.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[F:40][C:37]([F:38])([F:39])[O:36][C:32]1[CH:31]=[C:30]([C:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([O:15][C:14]([F:42])([F:41])[F:13])[CH:17]=2)=[N:23][S@@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[CH:35]=[CH:34][CH:33]=1.[CH3:29][C:26]([S:24]([NH:23][C:22]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:40])([F:38])[F:39])[CH:31]=1)([C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([O:15][C:14]([F:13])([F:42])[F:41])[CH:17]=1)[CH2:7][C:5]1[O:4][N:3]=[C:2]([CH3:1])[CH:6]=1)=[O:25])([CH3:27])[CH3:28]

Participants

8

Reactant 4

HCID 93123,5-DimethylisoxazoleHCID 25517Ammonium ChlorideHCID 72291066HCID 72291066, compoundHCID 178418339Butyllithium

Product 2

HCID 59458920(R)-N-(bis(3-(trifluoromethoxy)phenyl)-methylene)-2-methylpropane-2-sulfinamideHCID 72291098HCID 72291098, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

(R)—N-(bis(3-(trifluoromethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide was prepared as described for Procedure 11. Under an Argon atmosphere, 3,5-dimethylisoxazole (0.20 mL) was stirred in anhydrous THF in an oven-dried round bottomed flask at −78° C. nBuLi (2.5 M in hexanes, 0.84 mL, 2.1 mmol) was added dropwise. The resulting yellowish solution was stirred at −78° C. for 2 h. N-(bis(3-(trifluoromethoxy)phenyl)methylene)-2-methylpropane-2-sulfinamide (0.81 g, 1.8 mmol) in THF (2 mL) was added dropwise to the above stirred solution. The reaction mixture was stirred at −78° C. for 5 h, then slowly warmed up to room temperature overnight. Saturated NH4Cl was added, followed by the addition of EtOAc. The organic layer was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica gel, EtOAc/Hexanes=0 to 100%, came out at 100% EtOAc) to give 2-methyl-N-(2-(3-methylisoxazol-5-yl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)propane-2-sulfinamide as light tan viscous oil (0.14 g, yield: 13.5% with 0.55 g recovery of the starting material). LC-MS (ESI) 551.38 (M+H), retention time=3.98 min (10-90% MeOH in H2O with 0.1% TFA in a 4-min run); 1H NMR (400 MHz, CDCl3) δ ppm 7.49-7.40 (m, 2H), 7.37-7.28 (m, 1H), 7.19 (d, J=6.57 Hz, 1H), 7.05-7.14 (m, 4H), 5.70 (s, 1H), 4.61 (s, 1H), 4.14 (d, J=14.40 Hz, 1H), 3.88 (d, J=14.40 Hz, 1H), 2.26 (s, 2H), 2.13 (s, 3H), 1.26 (s, 9H).

Workup

  1. additionwas added dropwise
  2. stirringThe reaction mixture was stirred at −78° C. for 5 h
  3. temperatureslowly warmed up to room temperature overnight
  4. washThe organic layer was washed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by flash chromatography (silica gel, EtOAc/Hexanes=0 to 100%

Sources & evidence

ORD record
ord-46186a7bb43a4f5b977a7bec3cb81365
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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