Phenyl N-hydroxycarbamate → 4-{(3,5-Dimethyl-pyridin-2-ylmethyl)-[3-(1-methyl-1-phenyl-ethyl)-pyridin-2-ylmethyl]-amino}-piperidine-1-carboxylic acid

HRID 251196Notes

Reaction equation

HRID 251196 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([C:24]([CH3:32])([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[O:33]([C:40](NO)=[O:41])C1C=CC=CC=1>C1COCC1>[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([C:24]([CH3:32])([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:12][CH2:13][N:14]([C:40]([OH:41])=[O:33])[CH2:15][CH2:16]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

4

Reactant 2

HCID 148233Phenyl N-hydroxycarbamateHCID 67272593(3,5-Dimethyl-pyridin-2-ylmethyl)-[3-(1-methyl-1-phenyl-ethyl)-pyridin-2-ylmethyl]-piperidin-4-yl-amine

Product 1

HCID 692948054-{(3,5-Dimethyl-pyridin-2-ylmethyl)-[3-(1-methyl-1-phenyl-ethyl)-pyridin-2-ylmethyl]-amino}-piperidine-1-carboxylic acidYield 84.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of (3,5-dimethyl-pyridin-2-ylmethyl)-[3-(1-methyl-1-phenyl-ethyl)-pyridin-2-ylmethyl]-piperidin-4-yl-amine (1.20 g, 2.8 mmol) and N-(phenoxycarbonyl)-hydroxylamine (515 mg, 3.4 mmol) in THF (28 mL) was heated at reflux for 16 hours. The mixture was cooled to room temperature, concentrated, and purified on a silica gel column (40 g, eluted with 5% NH4OH/10% MeOH/CH3CN) to afford COMPOUND 350 (1.12 g, 82%), as a white solid. 1H NMR (CDCl3) δ 1.10-1.26 (m, 2H), 1.51 (d, 2H, J=11.5 Hz), 1.62 (s, 6H), 2.23 (s, 3H), 2.25 (s, 3H), 2.48 (t, 3H, J=11.5), 3.41 (s, 2H), 3.60 (s, 2H), 3.86 (d, 2H, J=12.0 Hz), 7.03 (d, 2H, J=7.5 Hz), 7.12-7.25 (m, 5H), 7.87 (d, 1H, J=8.0 Hz), 8.10 (s, 1H), 8.50 (d, 1H, J=3.5 Hz); 13C NMR (CDCl3) δ 18.31, 18.76, 27.73(2), 31.23 (2), 42.86, 43.94(2), 54.18, 54.78, 58.20, 121.96, 126.15(2), 126.42, 128.93(2), 131.98, 133.14, 134.44, 139.45, 143.75, 146.51, 146.89, 149.75, 161.05; ES-MS m/z 488 (M+H). Anal. Calcd. For C29H37N5O2.0.6H2O: C, 69.88; H, 7.72; N, 14.05. Found: C, 69.51; H, 7.55; N, 14.12.

Workup

  1. temperatureat reflux for 16 hours
  2. concentrationconcentrated
  3. custompurified on a silica gel column (40 g, eluted with 5% NH4OH/10% MeOH/CH3CN)

Sources & evidence

ORD record
ord-8372660650b24372afc161e9701fe258
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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