Cyclopentanol → Methyl 5-bromo-6-(cyclopentyloxy)nicotinate

HRID 1929812Notes

Reaction equation

HRID 1929812 reaction equation
[CH:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:9][O:10][C:11]([C:13]1[CH:14]=[N:15][C:16](Cl)=[C:17]([Br:19])[CH:18]=1)=[O:12]>CN(C=O)C>[CH3:9][O:10][C:11]([C:13]1[CH:14]=[N:15][C:16]([O:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[C:17]([Br:19])[CH:18]=1)=[O:12]

Participants

5

Reactant 3

HCID 7298CyclopentanolHCID 24758Sodium hydrideHCID 2764313Methyl 5-bromo-6-chloronicotinate

Product 1

HCID 66844699Methyl 5-bromo-6-(cyclopentyloxy)nicotinateYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cyclopentanol (1 mL, 11 mmol) was dissolved in DMF (25 mL) and a dispersion of sodium hydride in oil (55-65%, 480 mg) was added at room temperature. The mixture was stirred for 1 h at room temperature and 5-bromo-6-chloro-3-pyridinecarboxylic acid methyl ester (2.5 g, 10 mmol) was added. Stirring was continued for 1 h at room temperature and the mixture was afterwards partitioned between water and diethyl ether. Organic phases were pooled, dried with MgSO4 and the solvent was evaporated. The residue was purified by column chromatography on silica (n-heptane/ethyl acetate 9:1) to yield 0.48 g of the title compound as a colorless oil, MS (EI) 299.0, 301.0 (M)+.

Workup

  1. stirringStirring
  2. waitwas continued for 1 h at room temperature
  3. customthe mixture was afterwards partitioned between water and diethyl ether
  4. dry with materialdried with MgSO4
  5. customthe solvent was evaporated
  6. customThe residue was purified by column chromatography on silica (n-heptane/ethyl acetate 9:1)

Sources & evidence

ORD record
ord-217277cdfd0b4051985cd8927a17b104
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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