4-Fluorobenzyl bromide → 1-(4-fluorobenzyl)-N-(5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-yl)piperidin-4-amine

HRID 1643493Notes

Reaction equation

HRID 1643493 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[CH:21]([NH:25][CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[CH2:20][CH2:19]4)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[F:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][N:29]2[CH2:30][CH2:31][CH:26]([NH:25][CH:21]3[C:22]4[C:18](=[CH:17][C:16]([O:15][CH:12]5[CH2:13][CH2:14][N:9]([C:6]6[CH:7]=[CH:8][C:3]([C:2]([F:1])([F:32])[F:33])=[CH:4][CH:5]=6)[CH2:10][CH2:11]5)=[CH:24][CH:23]=4)[CH2:19][CH2:20]3)[CH2:27][CH2:28]2)=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 680214-Fluorobenzyl bromideHCID 81531DiisopropylethylamineHCID 57765773N-(5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-yl)piperidin-4-amine

Product 1

HCID 577657531-(4-fluorobenzyl)-N-(5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-yl)piperidin-4-amineYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of N-(5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-yl)piperidin-4-amine.3HCl (0.06 g, 0.1 mmol) in anhydrous dimethylformamide (0.5 mL) at room temperature was added 1-bromomethyl-4-fluorobenzene (0.02 g, 0.1 mmol) and N,N-diisopropylethylamine (0.07 g, 0.5 mmol). The resulting mixture was stirred at room temperature overnight. After this time the mixture was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=20/1/0.05) to afford the title compound as a off-white solid (0.05 g, 88%). 1H NMR (CDCl3, 300 MHz) 7.46 (m, 2H), 7.25 (m, 3H), 6.96 (m, 4H), 6.75 (m, 2H), 4.47 (m, 1H), 4.29 (m, 1H), 3.58 (m, 2H), 3.48 (s, 2H), 3.06-2.54 (m, 6H), 2.38 (m, 1H), 2.14-1.74 (m, 9H), 1.49 (m, 2H) ppm; MS (ES) 568.6 (M+H).

Workup

  1. concentrationAfter this time the mixture was concentrated under reduced pressure
  2. customthe resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=20/1/0.05)

Sources & evidence

ORD record
ord-d7a01d3126ae4ceba8da606a72cf2c7a
Source dataset
uspto-grants-2012_02
Patent number
US08119809B2

Reaction notes

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