Water → 2-(5-Bromo-pyridin-2-yl)-5-chloro-pentanoic acid methyl ester

HRID 220201Notes

Reaction equation

HRID 220201 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][N:8]=1.[Cl:15][CH2:16][CH2:17][CH2:18]Br.O>CN(C=O)C>[CH3:3][O:4][C:5](=[O:14])[CH:6]([C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][N:8]=1)[CH2:18][CH2:17][CH2:16][Cl:15]

Participants

6

Reactant 4

HCID 962WaterHCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 53419526Methyl 2-(5-broMopyridin-2-yl)acetate

Product 1

HCID 592382862-(5-Bromo-pyridin-2-yl)-5-chloro-pentanoic acid methyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (60%, 1.8 g, 44.9 mmol) dispersion in a mixture of DMF (60 mL), (5-Bromo-pyridin-2-yl)-acetic acid methyl ester (8.6 g, 37.4 mmol) was added under N2. After stirring and cooling on ice for 1 h, 3-chloro-1-propyl bromide (7.07 g, 44.9 mmol) was added dropwise and stirring was continued for 30 min under 10 degrees Celsius, then water was added and the mixture and extracted with EtOAc. The organic layer was dried (MgSO4) and evaporated in vacuo. The oily residue was purified by chromatography (Petroleum ether:EtOAc=15:1) to give an oil (6.87 g, 60%). MS: calc'd 305 (MH+), exp 305 (MH+). 1H NMR (400 MHz, CDCl3-d) 8.64 (d, 1H, J=2.4 Hz), 7.84 (dd, 1H, J=2.4, 8.4 Hz), 7.28 (s, 1H), 3.90-3.84 (m, 1H), 3.71 (s, 3H), 3.55 (t, 2H, J=6.4 Hz), 2.32-2.20 (m, 1H), 2.14-2.05 (m, 1H), 1.88-1.67 (m, 2H).

Workup

  1. additionwas added under N2
  2. temperaturecooling on ice for 1 h
  3. stirringstirring
  4. extractionthe mixture and extracted with EtOAc
  5. dry with materialThe organic layer was dried (MgSO4)
  6. customevaporated in vacuo
  7. customThe oily residue was purified by chromatography (Petroleum ether:EtOAc=15:1)

Sources & evidence

ORD record
ord-466328e05f24438e8a21a9ccd93260cd
Source dataset
uspto-grants-2012_06
Patent number
US08202866B2

Reaction notes

Loading…