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 705521Notes

Reaction equation

HRID 705521 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-8756a70e7ead4df9887b283fc664900c
Source dataset
uspto-grants-2015_11
Patent number
US09174964B2

Reaction notes

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