Boron trifluoride etherate → 8-Benzyloxy-5-(2-bromoacetyl)-2-hydroxyquinoline

HRID 724562Notes

Reaction equation

HRID 724562 reaction equation
[C:1]([C:4]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](=[O:22])[NH:9]2)(=[O:3])[CH3:2].B(F)(F)F.CCOCC.[Br:32]Br>ClCCl>[CH2:15]([O:14][C:11]1[CH:12]=[CH:13][C:4]([C:1](=[O:3])[CH2:2][Br:32])=[C:5]2[C:10]=1[NH:9][C:8](=[O:22])[CH:7]=[CH:6]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 24408BromineHCID 133754445-Acetyl-8-(benzyloxy)-1,2-dihydroquinolin-2-one

Product 1

HCID 116678678-Benzyloxy-5-(2-bromoacetyl)-2-hydroxyquinolineYield 134.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

5-Acetyl-8-benzyloxy-1H-quinolin-2-one (Preparation 6) (20.0 g, 68.2 mmol) was dissolved in dichloromethane (200 mL) and cooled to 0° C. Boron trifluoride diethyl etherate (10.4 mL, 82.0 mmol) was added via syringe and the mixture was warmed to room temperature to give a thick suspension. The suspension was heated at 45° C. (oil bath) and a solution of bromine (11.5 g, 72.0 mmol) in dichloromethane (100 mL) was added over 40 min. The mixture was kept at 45° C. for an additional 15 min and then cooled to room temperature. The mixture was concentrated under reduced pressure and then triturated with 10% aqueous sodium carbonate (200 mL) for 1 hour. The solids were collected on a Buchner funnel, washed with water (4×100 mL) and dried under reduced pressure. The product of two runs was combined for purification. The crude product (52 g) was triturated with 50% methanol in chloroform (500 mL) for 1 hour. The product was collected on a Buchner funnel and washed with 50% methanol in chloroform (2×50 mL) and methanol (2×50 mL). The solid was dried under reduced pressure to give the title compound (34.1 g) as a powder.

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. customto give a thick suspension
  3. temperatureThe suspension was heated at 45° C. (oil bath)
  4. temperaturecooled to room temperature
  5. concentrationThe mixture was concentrated under reduced pressure
  6. customtriturated with 10% aqueous sodium carbonate (200 mL) for 1 hour
  7. customThe solids were collected on a Buchner funnel
  8. washwashed with water (4×100 mL)
  9. customdried under reduced pressure
  10. customThe product of two runs was combined for purification
  11. customThe crude product (52 g) was triturated with 50% methanol in chloroform (500 mL) for 1 hour
  12. customThe product was collected on a Buchner funnel
  13. washwashed with 50% methanol in chloroform (2×50 mL) and methanol (2×50 mL)
  14. customThe solid was dried under reduced pressure

Sources & evidence

ORD record
ord-db77ff6670254b9480dba3e991ef9dd0
Source dataset
uspto-grants-2006_11
Patent number
US07141671B2

Reaction notes

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