Isobutyryl chloride → N-(4-{1-[(3R)-3-(3,4-Dimethoxyphenoxy)-3-Phenylpropyl]-4-Piperidinyl}Phenyl)-2-Methylpropanamide

HRID 1832204Notes

Reaction equation

HRID 1832204 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][CH3:33])[O:6][C@@H:7]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1.[C:34](Cl)(=[O:38])[CH:35]([CH3:37])[CH3:36].C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[O:32][CH3:33])[O:6][C@@H:7]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:8][CH2:9][N:10]1[CH2:11][CH2:12][CH:13]([C:16]2[CH:22]=[CH:21][C:19]([NH:20][C:34](=[O:38])[CH:35]([CH3:37])[CH3:36])=[CH:18][CH:17]=2)[CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 695235024-{1-[(3R)-3-(3,4-Dimethoxyphenoxy)-3-Phenylpropyl]-4-Piperidinyl}Aniline

Product 1

HCID 60078710N-(4-{1-[(3R)-3-(3,4-Dimethoxyphenoxy)-3-Phenylpropyl]-4-Piperidinyl}Phenyl)-2-MethylpropanamideYield 56.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-{1-[(3R)-3-(3,4-dimethoxyphenoxy)-3-phenylpropyl]-4-piperidinyl}aniline (5.31 mg, 0.0119 mmol), isobutyryl chloride (2.08 mg, 0.019 mmol), N,N-diisopropylethylamine (8.40 mg, 0.0650 mmol) in methylene chloride (1.0 mL) was stirred at room temperature for 24 hours. The reaction mixture was concentrated and chromatographed using a preparative TLC plate [2.5% of NH3 (2.0 M in methanol) in CHCl3] to give the product (3.5 mg, 56.5%) as a thick oil: 1H NMR (400 MHz, CDCl3) δ 7.38 (d, 1H, J=8.6 Hz), 7.30–7.20 (m, 4H), 7.20 (m, 1H), 7.11 (d, 2H, J=8.6 Hz), 7.04 (s, 1H), 6.57 (d, 1H, J=8.3 Hz), 6.44 (d, 1H, J=2.6 Hz), 6.22 (dd, 1H, J=2.6, 8.3 Hz), 5.09 (apparent dd, 1H, J=4.4, 8.1 Hz), 3.72 (s, 3H), 3.70 (s, 3H), 3.08 (m, 2H), 2.57 (m, 2H), 2.43 (apparent sept, partially hidden, 2H, J=6.8 Hz), 2.30–2.10 (m, 6H), 1.80 (m, 2H), 1.25 (d, 6H, J=7.9 Hz); ESMS m/e: 517.3 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customchromatographed

Sources & evidence

ORD record
ord-3ac050968e5a46879e5ce1e5a700f701
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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