Ethyl Acetate → N-Boc 4-{[(2-bromo-4-cyanophenyl)acetyl]amino}piperidine

HRID 2060047Notes

Reaction equation

HRID 2060047 reaction equation
[Br:1][C:2]1[CH:3]=C(CC(O)=O)C=[CH:6][C:7]=1C#N.[C:14]([N:21]1[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]1)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].CCN=C=N[CH2:33][CH2:34][CH2:35][N:36](C)C.Cl.C(N(C(C)C)CC)(C)C.C([O:52][CH2:53][CH3:54])(=O)C>CN(C=O)C>[C:14]([N:21]1[CH2:26][CH2:25][CH:24]([NH:27][C:53](=[O:52])[CH2:54][C:7]2[CH:6]=[CH:33][C:34]([C:35]#[N:36])=[CH:3][C:2]=2[Br:1])[CH2:23][CH2:22]1)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

Participants

7

Reactant 5

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665249442-(3-Bromo-4-cyanophenyl)acetic acid

Product 1

HCID 59444100N-Boc 4-{[(2-bromo-4-cyanophenyl)acetyl]amino}piperidineYield 40.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-bromo-4-cyanophenylacetic acid (D134, 2.1 g, 7.00 mmol), 1-Boc 4-aminopiperidine (1.5 g, 7.49 mmol), EDC hydrochloride (1.5 g, 7.82 mmol), diisopropylethylamine (3.0 mL, 17.22 mmol), and DMF (25 mL) was stirred for 2 h at room temperature then diluted with ethyl acetate and washed with aqueous citric acid, aqueous sodium bicarbonate, water, and brine. Crystallisation from diethyl ether gave N-Boc 4-{[(2-bromo-4-cyanophenyl)acetyl]amino}piperidine (1.5 g, 2.84 mmol, 40.6% yield) as a white solid containing about 20% of N-Boc 4-{[(4-cyanophenyl)acetyl]amino}piperidine.

Workup

  1. washwashed with aqueous citric acid, aqueous sodium bicarbonate, water, and brine
  2. customCrystallisation from diethyl ether

Sources & evidence

ORD record
ord-e49f81a0bca94498a067dad1adcbea92
Source dataset
uspto-grants-2012_10
Patent number
US08278328B2

Reaction notes

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