Phosphorus oxychloride → 1-(6-Bromo-4-chloroquinolin-3-yl)-3-methylbutan-1-one

HRID 2271521Notes

Reaction equation

HRID 2271521 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:17])[CH2:13][CH:14]([CH3:16])[CH3:15])=[C:5]2O.P(Cl)(Cl)([Cl:21])=O.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:17])[CH2:13][CH:14]([CH3:16])[CH3:15])=[C:5]2[Cl:21]

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 86584982Sodium bicarbonate ethyl acetateHCID 178446973HCID 178446973, compound

Product 1

HCID 866928431-(6-Bromo-4-chloroquinolin-3-yl)-3-methylbutan-1-oneYield 98%

Conditions

Temperature
85 °C

Procedure

1-(6-Bromo-4-hydroxyquinolin-3-yl)-3-methylbutan-1-one (300 mg, 0.970 mmol) was added to phosphoryl chloride (9.7 mL) and the reaction was stirred at 85° C. for 1 h. After this time the reaction mixture was cooled to room temperature and slowly poured into a 2:1 solution of satd. aq. sodium bicarbonate/ethyl acetate that was cooled to 0° C. The organic layer was separated and was washed with satd. aq. sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford the desired product (309 mg, 98%) as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 8.86 (s, 1H), 8.51 (d, J=2.0 Hz, 1H), 8.01 (d, J=8.9 Hz, 1H), 7.91 (dd, J=8.9, 2.0 Hz, 1H), 2.96 (d, J=6.9 Hz, 2H), 2.39-2.23 (m, 1H), 1.03 (d, J=6.7 Hz, 6H).

Workup

  1. temperatureAfter this time the reaction mixture was cooled to room temperature
  2. additionslowly poured into a 2:1 solution of satd
  3. customThe organic layer was separated
  4. washwas washed with satd
  5. dry with materialaq. sodium bicarbonate, dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-69bcba8cbf434d79aa3a6204058a227e
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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