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 1046517Notes

Reaction equation

HRID 1046517 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-be3bb009223c44c9852fb54725270d31
Source dataset
uspto-grants-2013_10
Patent number
US08569340B2

Reaction notes

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