N-Methylbenzylamine → HCID 86751320, compound

HRID 1418580Notes

Reaction equation

HRID 1418580 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:17])[CH2:15][Cl:16])[CH2:10][C@H:9]1[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([CH3:26])[CH:20]=1)=[O:7].[CH3:36][NH:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>O1CCCC1>[ClH:16].[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:17])[CH2:15][N:37]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH3:36])[CH2:10][C@H:9]1[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([CH3:26])[CH:20]=1)=[O:7]

Participants

4

Reactant 2

HCID 7669N-Methylbenzylamine2×HCID 86751322HCID 86751322, compound

Product 1

HCID 86751320HCID 86751320, compoundYield 94.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a stirred solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(2-chloroacetyl)piperazine (300 mg) in tetrahydrofuran (5 ml) was added N-methylbenzylamine (140 mg) at room temperature. After stirring for 2 hours, additional N-methylbenzylamine (70 mg) was added, and then the whole was heated at 45° C. for 6 hours. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate (20 ml) and aqueous sodium bicarbonate solution (10 ml). The organic layer was separated and dried over magnesium sulfate. After evaporation of the solvent in vacuo, the residue was purified by column chromatography on a silica gel eluting with a mixture of dichloromethane and methanol (50:1) and treated with 4N hydrogen chloride in ethyl acetate solution to afford (2R)-1-[3,5-bis(trifluoromethyl)-benzoyl]-4-[2-(N-benzyl-N-methylamino)acetyl]-2-(3,4-dimethylbenzyl)piperazine hydrochloride (0.35 g).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate (20 ml) and aqueous sodium bicarbonate solution (10 ml)
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. customAfter evaporation of the solvent in vacuo
  6. customthe residue was purified by column chromatography on a silica gel eluting with a mixture of dichloromethane and methanol (50:1)
  7. additiontreated with 4N hydrogen chloride in ethyl acetate solution

Sources & evidence

ORD record
ord-524a9a50b3724b44af2c85d6691eda69
Source dataset
uspto-grants-1999_03
Patent number
US05883098

Reaction notes

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