2-Bromoisovaleric acid → 2-Bromo-1-(4-(4-chlorophenyl)piperidin-1-yl)-3-methylbutan-1-one

HRID 1016114Notes

Reaction equation

HRID 1016114 reaction equation
[Br:1][CH:2]([CH:6]([CH3:8])[CH3:7])[C:3](O)=[O:4].Cl.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>CN(C=O)C.CCOCC>[Br:1][CH:2]([CH:6]([CH3:8])[CH3:7])[C:3]([N:20]1[CH2:21][CH2:22][CH:17]([C:14]2[CH:13]=[CH:12][C:11]([Cl:10])=[CH:16][CH:15]=2)[CH2:18][CH2:19]1)=[O:4]

Participants

8

Reactant 5

HCID 112682-Bromoisovaleric acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27578434-(4-chlorophenyl)piperidine Hydrochloride

Product 1

HCID 578896732-Bromo-1-(4-(4-chlorophenyl)piperidin-1-yl)-3-methylbutan-1-oneYield 85%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-bromo-3-methylbutanoic acid (14) (400 mg, 2.2 mmol), 4-(4-chlorophenyl)-piperidine hydrochloride (500 mg, 2.2 mmol), HOBt (300 mg, 2.2 mmol) and EDCI (425 mg, 2.2 mmol) was suspended in DMF (10 mL). DIEA (1.4 mL, 8 mmol) was added and the reaction was stirred overnight. After this time, the reaction was diluted with Et2O (100 mL) and washed sequentially with H2O (2×40 mL); aqueous 1N HCl (2×20 mL); aqueous sat. NaHCO3 (1×20 mL) solution and aqueous sat. NaCl (1×20 mL) solution. The Et2O layer was dried (MgSO4), and the solvents were removed to give 2-bromo-1-(4-(4-chlorophenyl)piperidin-1-yl)-3-methylbutan-1-one (600 mg, 85%) as an impure oil, which was used without purification. MS found: 360 (M+H).

Workup

  1. washwashed sequentially with H2O (2×40 mL)
  2. dry with materialThe Et2O layer was dried (MgSO4)
  3. customthe solvents were removed

Sources & evidence

ORD record
ord-b50da7b920fc4c96a55c23143d0e00f6
Source dataset
uspto-grants-2011_07
Patent number
US07985861B2

Reaction notes

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