Benzyl Bromide → 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

HRID 1629791Notes

Reaction equation

HRID 1629791 reaction equation
[CH3:1][C:2]([S:5]([NH:7][C:8]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][CH2:33][C:34]([F:37])([F:36])[F:35])=[CH:26][CH:25]=1)([C:13]([F:23])([F:22])[C:14](=[O:21])[N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:9]([F:12])([F:11])[F:10])=[O:6])([CH3:4])[CH3:3].[H-].[Na+].[CH:40]1[CH:45]=[CH:44][C:43]([CH2:46]Br)=[CH:42][CH:41]=1>CN(C=O)C.CCOC(C)=O>[CH2:46]([N:7]([C:8]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][CH2:33][C:34]([F:37])([F:35])[F:36])=[CH:26][CH:25]=1)([C:13]([F:22])([F:23])[C:14](=[O:21])[N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:9]([F:10])([F:11])[F:12])[S:5]([C:2]([CH3:1])([CH3:3])[CH3:4])=[O:6])[C:43]1[CH:44]=[CH:45][CH:40]=[CH:41][CH:42]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 866858832-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

Product 1

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-sulfinamideYield 48.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Intermediate 103D (461 mg, 0.814 mmol) in anhydrous DMF (0.5 mL) was added to a suspension of NaH (65 mg, 1.627 mmol) (60% in mineral oil) at 0° C. After stirring for 5 min, BnBr (0.484 mL, 4.07 mmol) was added. The reaction mixture was warmed to rt and stirred for 1 h. The reaction was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography (4 g silica gel, eluted with EtOAc in hexanes) to yield the desired product (260 mg, 44%) as a yellow gum. 1H NMR (500 MHz, CDCl3) δ 7.75 (d, J=8.5 Hz, 2H), 7.33-7.27 (m, 3H), 7.14 (dd, J=7.3, 2.1 Hz, 2H), 6.80 (d, J=9.1 Hz, 2H), 4.46-4.38 (m, 2H), 4.00-3.95 (m, 2H), 3.72 (br. s., 1H), 3.51 (br. s., 1H), 3.35-3.10 (m, 2H), 2.37-2.25 (m, 2H), 2.09-1.99 (m, 2H), 1.70-1.39 (m, 6H), 1.34-1.29 (m, 9H).

Workup

  1. stirringstirred for 1 h
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (4 g silica gel, eluted with EtOAc in hexanes)

Sources & evidence

ORD record
ord-1435b2f980244b7db752d8955041bf92
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

Loading…