Pyridine → (3-Bromo-7-fluoro-quinolin-6-yl)-acetic acid methyl ester

HRID 655252Notes

Reaction equation

HRID 655252 reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[F:15])[N:11]=[CH:10][CH:9]=[CH:8]2.N1C=CC=CC=1.[Br:23]Br>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[F:15])[N:11]=[CH:10][C:9]([Br:23])=[CH:8]2

Participants

5

Reactant 3

HCID 1049PyridineHCID 24408BromineHCID 59320292(7-Fluoro-quinolin-6-yl)-acetic acid methyl ester

Product 1

HCID 68706227(3-Bromo-7-fluoro-quinolin-6-yl)-acetic acid methyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

To a mixture of (7-fluoro-quinolin-6-yl)-acetic acid methyl ester (14.0 g, 63.9 mmol) and pyridine (10.4 mL, 127.8 mmol) in 200 mL of carbon tetrachloride was added bromine (6.6 mL, 127.8 mmol) in a dropwise fashion. The mixture was heated to reflux for 2 hrs before being cooled to ambient temperature. The liquid in the flask was decanted and washed with NaHCO3 and water. The dark solid on the bottom of the flask was treated with NaHCO3 and dichloromethane. The combined organic layers were washed with water, dried (Na2SO4) and evaporated to dryness. The crude product was purified via flash column chromatography eluting with petroleum ether/ethyl acetate (40/1˜3/1) to return 13.9 g (75% yield) of the title compound as white crystalline solid. 1H NMR (DMSO-d6): δ 8.89 (s, 1H), 8.27 (m, 1H), 7.66˜7.74 (m, 2H), 3.87 (s, 2H), 3.74 (s, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 hrs
  3. customThe liquid in the flask was decanted
  4. washwashed with NaHCO3 and water
  5. additionThe dark solid on the bottom of the flask was treated with NaHCO3 and dichloromethane
  6. washThe combined organic layers were washed with water
  7. dry with materialdried (Na2SO4)
  8. customevaporated to dryness
  9. customThe crude product was purified via flash column chromatography
  10. washeluting with petroleum ether/ethyl acetate (40/1˜3/1)

Sources & evidence

ORD record
ord-678e4e7d32e841f6a4430c1f3bc5960d
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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