3,4-Methylenedioxybenzyl-(3-azepin-1-yl-propyl)-amine → 3,4-Methylenedioxybenzyl-[3-(3,5-difluorophenyl)-isoxazol-5-yl]-(3-azepin-1-yl-propyl)-amine hydrochloride

HRID 1264531Notes

Reaction equation

HRID 1264531 reaction equation
[CH2:1]1[O:21][C:20]2[CH:19]=[CH:18][C:5]([CH2:6][NH:7][CH2:8][CH2:9][CH2:10][N:11]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=[CH:12]3)=[CH:4][C:3]=2[O:2]1.[Li]CCCC.[F:27][C:28]1[CH:29]=[C:30]([C:35]2[CH:39]=[C:38]([Cl:40])[O:37][N:36]=2)[CH:31]=[C:32]([F:34])[CH:33]=1>C(OCC)C.CCCCCC.C(OCC)(=O)C>[ClH:40].[CH2:1]1[O:21][C:20]2[CH:19]=[CH:18][C:5]([CH2:6][N:7]([C:38]3[O:37][N:36]=[C:35]([C:30]4[CH:29]=[C:28]([F:27])[CH:33]=[C:32]([F:34])[CH:31]=4)[CH:39]=3)[CH2:8][CH2:9][CH2:10][N:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=[CH:17]3)=[CH:4][C:3]=2[O:2]1

Participants

7

Reactant 3

HCID 186126483,4-Methylenedioxybenzyl-(3-azepin-1-yl-propyl)-amineHCID 186126645-Chloro-3-(3,5-difluorophenyl)isoxazoleHCID 178418339Butyllithium

Product 1

HCID 186126573,4-Methylenedioxybenzyl-[3-(3,5-difluorophenyl)-isoxazol-5-yl]-(3-azepin-1-yl-propyl)-amine hydrochloride

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3,4-methylenedioxybenzyl-(3-azepin-1-yl-propyl)amine in diethyl ether (26.7 ml of a 0.12 M solution in diethyl ether, 3.22 mmol) cooled to 0° C. is slowly added n-BuLi (1.51 ml of a 1.6M solution in hexane, 2.41 mmol). The resulting mixture is stirred at 0° C. for 10 min and 3-(3,5-difluorophenyl)-5-chloroisoxazole (347 mg, 1.61 mmol) is added at once. After stirring at 0° C. for 30 min, the reaction mixture is dilute with ethyl acetate, washed with water andbrine, dried over sodium sulfate, and concentrated in vacuo. The crude material is purified by flash chromatography (silica gel, 3% methanol containing 10% NH4OH in dichloromethane) to give the free base of the title compound as an oil. The free base is dissolved in dichloromethane (10 ml) and treated with 1 N HCl in diethyl ether (4 ml, 4 mmol) to provide after concentration in vacuo, 3,4-methylenedioxybenzyl-[3-(3,5-difluorophenyl)-isoxazol-5-yl]-(3-azepin-1-yl-propyl)-amine hydrochloride (513 mg, 63%) as a pale yellow foam.

Workup

  1. stirringAfter stirring at 0° C. for 30 min
  2. washwashed with water andbrine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude material is purified by flash chromatography (silica gel, 3% methanol containing 10% NH4OH in dichloromethane)

Sources & evidence

ORD record
ord-0f8ae4ef8613414fbf37bfc0bd0e4e30
Source dataset
uspto-grants-2003_04
Patent number
US06544982B1

Reaction notes

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