Diisopropylethylamine → Ethyl 1-(5-bromopyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

HRID 1399970Notes

Reaction equation

HRID 1399970 reaction equation
Cl.[CH3:2][C:3]1([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.CCN(C(C)C)C(C)C.[Br:23][C:24]1[CH:25]=[N:26][C:27](Cl)=[N:28][CH:29]=1>CCO>[Br:23][C:24]1[CH:25]=[N:26][C:27]([N:6]2[CH2:7][CH2:8][C:3]([CH3:2])([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:5]2)=[N:28][CH:29]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 19361804Ethyl 4-methylpiperidine-4-carboxylate hydrochloride

Product 1

HCID 66977024Ethyl 1-(5-bromopyrimidin-2-yl)-4-methylpiperidine-4-carboxylateYield 76.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ii (0.9 g, 4.35 mmol) in EtOH (10 mL) was added DIPEA (2.30 mL, 13 mmol) at RT and the mixture stirred at RT for 10 min followed by addition of 5-bromo-2-chloropyrimidine (0.7 g, 3.6 mmol). The mixture was heated at 70° C. for 1 h. The solvent was evaporated and the crude residue purified by chromatography on silica eluting with 1.5% EtOAc:hexane to obtain iii (0.90 g, 75%). 1H NMR (DMSO-d6, 400 MHz): δ 1.17 (s, 3H), 1.21 (t, J=7.20 Hz, 3H) 1.40 (m, 2H), 2.00 (m, 2H), 3.24 (m, 2H), 4.11 (m, 2H), 4.15 (q, J=7.20 Hz, 2H), 8.43 (s, 2H). MS: 328.08 [M+H]+.

Workup

  1. temperatureThe mixture was heated at 70° C. for 1 h
  2. customThe solvent was evaporated
  3. customthe crude residue purified by chromatography on silica eluting with 1.5% EtOAc

Sources & evidence

ORD record
ord-49677a918e764ddf96968cc13f1ac9b6
Source dataset
uspto-grants-2014_12
Patent number
US08906902B2

Reaction notes

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