Hydrogen Bromide → 4-(1-(5-(2-Bromoacetyl)-4-cyclobutyl-2-methylbenzoyl)piperidin-4-yl)benzonitrile

HRID 541388Notes

Reaction equation

HRID 541388 reaction equation
[Si](C=[N+]=[N-])(C)(C)[CH3:2].[C:8]([C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([C:24]3[C:25]([CH3:37])=[CH:26][C:27]([CH:33]4[CH2:36][CH2:35][CH2:34]4)=[C:28]([CH:32]=3)[C:29](Cl)=[O:30])=[O:23])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)#[N:9].[BrH:38]>ClCCl>[Br:38][CH2:2][C:29]([C:28]1[C:27]([CH:33]2[CH2:36][CH2:35][CH2:34]2)=[CH:26][C:25]([CH3:37])=[C:24]([CH:32]=1)[C:22]([N:19]1[CH2:20][CH2:21][CH:16]([C:13]2[CH:14]=[CH:15][C:10]([C:8]#[N:9])=[CH:11][CH:12]=2)[CH2:17][CH2:18]1)=[O:23])=[O:30]

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 167693TrimethylsilyldiazomethaneHCID 866725405-(4-(4-Cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-methylbenzoyl chloride2×

Product 1

HCID 866725414-(1-(5-(2-Bromoacetyl)-4-cyclobutyl-2-methylbenzoyl)piperidin-4-yl)benzonitrileYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

To a solution of TMSCHN2 (2 M in hexane) (0.476 mL, 2.00 equiv) in dichloromethane (10 mL) under nitrogen at 0° C. was added dropwise a solution of 5-(4-(4-cyanophenyl)piperidine-1-carbonyl)-2-cyclobutyl-4-methylbenzoyl chloride (compound 235.1, 200 mg, 0.480 mmol, 1.00 equiv) in dichloromethane (3 mL). The resulting mixture was stirred overnight at 25° C. HBr (40%) (0.154 mL, 1.50 equiv) was then added dropwise at 0° C. and the mixture was stirred for another 2 h at 0° C., then diluted with 50 mL of dichloromethane. The organic layer was washed with 2×20 mL of water and 1×20 mL of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (0:1-1:50-1:5) as eluent to furnish 200 mg (88%) of 4-(1-(5-(2-bromoacetyl)-4-cyclobutyl-2-methylbenzoyl)piperidin-4-yl)benzonitrile as a yellow oil.

Workup

  1. stirringthe mixture was stirred for another 2 h at 0° C.
  2. washThe organic layer was washed with 2×20 mL of water and 1×20 mL of brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified

Sources & evidence

ORD record
ord-cb473a77941f401981696717093db267
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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