Hexane → Methyl 1-(5-bromopyrimidin-2-yl)-4-hydroxy-piperidine-4-carboxylate

HRID 712213Notes

Reaction equation

HRID 712213 reaction equation
[OH:1][C:2]1([C:8]([O:10][CH3:11])=[O:9])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.[Br:21][C:22]1[CH:23]=[N:24][C:25](Cl)=[N:26][CH:27]=1.CCCCCC>CCO>[Br:21][C:22]1[CH:23]=[N:24][C:25]([N:5]2[CH2:4][CH2:3][C:2]([OH:1])([C:8]([O:10][CH3:11])=[O:9])[CH2:7][CH2:6]2)=[N:26][CH:27]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 81531DiisopropylethylamineHCID 6066655-Bromo-2-chloropyrimidineHCID 21093366Methyl 4-hydroxypiperidine-4-carboxylate

Product 1

HCID 66977198Methyl 1-(5-bromopyrimidin-2-yl)-4-hydroxy-piperidine-4-carboxylateYield 44%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of methyl 4-hydroxypiperidine-4-carboxylate (0.4 g, 2.52 mmol) in EtOH (10 mL) was added DIPEA (2.2 mL, 12.57 mmol) and the solution stirred at rt for 10 min followed by addition of 5-bromo-2-chloropyrimidine (0.49 g, 2.52 mmol). The mixture was then 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 desired product as a yellow solid (0.35 g, 44% yield). 1H NMR (DMSO-d6): δ 1.64 (m, 2H), 1.82 (m, 2H), 3.20 (m, 2H), 3.64 (s, 3H), 4.27 (m, 2H), 5.60 (s, 1H) and 8.44 (s, 2H).

Workup

  1. temperatureThe mixture was then 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-036a534812504df19e64d4fc3347208d
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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