Hexane → Ethyl 1-(5-bromopyrimidin-2-yl)-4-cyano-piperidine-4-carboxylate

HRID 712209Notes

Reaction equation

HRID 712209 reaction equation
Cl.[C:2]([C:4]1([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)#[N:3].CCN(C(C)C)C(C)C.[Br:24][C:25]1[CH:26]=[N:27][C:28](Cl)=[N:29][CH:30]=1.CCCCCC>CCO>[Br:24][C:25]1[CH:26]=[N:27][C:28]([N:7]2[CH2:8][CH2:9][C:4]([C:2]#[N:3])([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:5][CH2:6]2)=[N:29][CH:30]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 14294360Ethyl 4-cyanopiperidine-4-carboxylate hydrochloride

Product 1

HCID 66977102Ethyl 1-(5-bromopyrimidin-2-yl)-4-cyano-piperidine-4-carboxylateYield 68.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 4-cyanopiperidine-4-carboxylate hydrochloride (0.56 g, 2.6 mmol) in EtOH (10 mL) was added DIPEA (0.8 mL, 4.29 mmol) at rt and stirred at rt for 10 min followed by addition of 5-bromo-2-chloropyrimidine (0.33 g, 1.73 mmol). The reaction mixture was heated up to 70° C. for 1 h. After completion of reaction (by TLC), solvent was evaporated and the crude residue purified over 100-200 M silica-gel using 10% EtOAc:hexane to obtain the product as a yellow solid (0.4 g, 68% yield). 1H NMR (DMSO-d6): δ 1.20 (t, J=7.20 Hz, 3H), 2.04 (m, 2H), 2.22 (m, 2H), 3.22 (m, 2H), 4.15 (q, J=7.20 Hz, 2H), 4.32 (m, 2H) and 8.50 (s, 2H).

Workup

  1. temperatureThe reaction mixture was heated up to 70° C. for 1 h
  2. customAfter completion of reaction (by TLC), solvent
  3. customwas evaporated
  4. customthe crude residue purified over 100-200 M silica-gel

Sources & evidence

ORD record
ord-faef35f483d34050ac48bb5be8863cf3
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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