N-Benzyl-2-methyl-N-(1,1,1,3,3-pentafluoro-4-oxo-4-(piperidin-1-yl)-2-(4-(4,4,4-trifluorobutoxy)phenyl)butan-2-yl)propane-2-sulfinamide → 2-Methyl-N-(1,1,1,3,3-pentafluoro-4-oxo-4-p-tolyl-2-(4-(4,4,4-trifluorobutoxy)phenyl)butan-2-yl)propane-2-sulfinamide

HRID 1629792Notes

Reaction equation

HRID 1629792 reaction equation
C([N:8]([C:15]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][C:41]([F:44])([F:43])[F:42])=[CH:33][CH:32]=1)([C:20]([F:30])([F:29])[C:21](=[O:28])N1CCCCC1)[C:16]([F:19])([F:18])[F:17])[S:9]([C:11]([CH3:14])([CH3:13])[CH3:12])=[O:10])C1C=CC=CC=1.[C:45]1([CH3:53])[CH:50]=[CH:49][C:48]([Mg]Br)=[CH:47][CH:46]=1>C1COCC1>[CH3:14][C:11]([S:9]([NH:8][C:15]([C:31]1[CH:32]=[CH:33][C:34]([O:37][CH2:38][CH2:39][CH2:40][C:41]([F:44])([F:42])[F:43])=[CH:35][CH:36]=1)([C:20]([F:30])([F:29])[C:21](=[O:28])[C:48]1[CH:49]=[CH:50][C:45]([CH3:53])=[CH:46][CH:47]=1)[C:16]([F:17])([F:18])[F:19])=[O:10])([CH3:12])[CH3:13]

Participants

4

Reactant 2

HCID 86685884N-Benzyl-2-methyl-N-(1,1,1,3,3-pentafluoro-4-oxo-4-(piperidin-1-yl)-2-(4-(4,4,4-trifluorobutoxy)phenyl)butan-2-yl)propane-2-sulfinamideHCID 178418370HCID 178418370, compound

Product 1

HCID 866858852-Methyl-N-(1,1,1,3,3-pentafluoro-4-oxo-4-p-tolyl-2-(4-(4,4,4-trifluorobutoxy)phenyl)butan-2-yl)propane-2-sulfinamideYield 26.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Mg turnings were suspended in 0.1 N aq HCl for a few minutes, rinsed with water, MeOH and dried under vacuum. A flame dried flask equipped with a stir bar was charged with Mg turnings (0.243 g, 10 mmol), anhydrous THF (4.4 mL) and 4-bromotoluene (1.71 g, 10 mmol) in anhydrous THF (4.4 mL) followed by several drops of 1,2-dibromoethane. The reaction initiated in a few minutes and the mixture became warm. The approximate concentration of the Grignard reagent is 1 M. The mixture was diluted with 10 mL anhydrous THF to produce a clear solution of p-tolylmagnesium bromide (˜0.5 M). To a solution of Intermediate 103E (260 mg, 0.396 mmol) in THF (3959 μL) at 0° C. was added the freshly prepared p-tolylmagnesium bromide (3959 μL, 1.980 mmol). The reaction was warmed to rt, concentrated to half of the original volume, and stirred for 3 h. The reaction was cooled to 0° C., quenched with sat'd aq NH4Cl, and then diluted with EtOAc. The layers were separated and the organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes) to afford the desired product (60 mg, 24%) as a yellow gum. 1H NMR (500 MHz, CDCl3) δ 7.73 (d, J=8.0 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H), 7.19 (d, J=8.0 Hz, 2H), 6.83 (d, J=8.8 Hz, 2H), 4.19 (s, 1H), 4.01 (br. s., 2H), 2.40 (s, 3H), 2.31 (dd, J=16.2, 10.2 Hz, 2H), 2.10-1.99 (m, 2H), 1.25 (s, 9H).

Workup

  1. concentrationconcentrated to half of the original volume
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched with sat'd aq NH4Cl
  4. additiondiluted with EtOAc
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes)

Sources & evidence

ORD record
ord-661f5724290741a89286084430e293f0
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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