p-METHYLACETOPHENONE → (S)-2-Methyl-N-((S)-1,1,1-trifluoro-4-oxo-4-p-tolyl-2-(4-(6,6,6-trifluorohexyloxy)phenyl)butan-2-yl)propane-2-sulfinamide

HRID 1629768Notes

Reaction equation

HRID 1629768 reaction equation
[C:1]1([CH3:10])[CH:6]=[CH:5][C:4]([C:7](=[O:9])[CH3:8])=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:21][C:22]([S@@:25](/[N:27]=[C:28](\[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][C:45]([F:48])([F:47])[F:46])=[CH:35][CH:34]=1)/[C:29]([F:32])([F:31])[F:30])=[O:26])([CH3:24])[CH3:23]>C1COCC1>[CH3:24][C:22]([S@@:25]([NH:27][C@:28]([C:33]1[CH:34]=[CH:35][C:36]([O:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][C:45]([F:48])([F:46])[F:47])=[CH:37][CH:38]=1)([CH2:8][C:7](=[O:9])[C:4]1[CH:5]=[CH:6][C:1]([CH3:10])=[CH:2][CH:3]=1)[C:29]([F:30])([F:32])[F:31])=[O:26])([CH3:21])[CH3:23]

Participants

5

Reactant 3

HCID 8500p-METHYLACETOPHENONEHCID 2733832Lithium HexamethyldisilazideHCID 89599581(NE,S)-2-methyl-N-[2,2,2-trifluoro-1-[4-(6,6,6-trifluorohexoxy)phenyl]ethylidene]propane-2-sulfinamide

Product 1

HCID 86685859(S)-2-Methyl-N-((S)-1,1,1-trifluoro-4-oxo-4-p-tolyl-2-(4-(6,6,6-trifluorohexyloxy)phenyl)butan-2-yl)propane-2-sulfinamideYield 59.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-(p-tolyl)ethanone (609 mg, 4.31 mmol) in THF (10 mL) was cooled to −78° C. and to this solution was added lithium bis(trimethylsilyl)amide (4.31 mL, 4.31 mmol). The resulting mixture was stirred at −78° C. for 20 min and then Intermediate 8C (620 mg, 1.437 mmol) in THF (3 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 1.5 h and then at 0° C. for 1.5 h. The reaction was quenched with NH4Cl and concentrated. The crude product was purified by silica gel chromatography (80 g silica gel, eluted with EtOAc in hexanes) to afford Intermediate 8D (482 mg, 59%) as the slower eluting diastereomer on silica gel column. LCMS Anal. Calc'd for C27H33F6NO3S 565.21, found [M+H] 566.0.

Workup

  1. stirringThe resulting mixture was stirred at −78° C. for 1.5 h
  2. waitat 0° C. for 1.5 h
  3. customThe reaction was quenched with NH4Cl
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (80 g silica gel, eluted with EtOAc in hexanes)

Sources & evidence

ORD record
ord-c7c3368b74e447cca38b901152a33ee6
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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