Toluene → 5-((1R)-2-bromo-1-hydroxyethyl)-8-phenylmethoxy-1H-quinolin-2-one

HRID 883630Notes

Reaction equation

HRID 883630 reaction equation
[Br:1][CH2:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:11]2[C:6]=1[CH:7]=[CH:8][C:9](=[O:23])[NH:10]2)=[O:4].C1(C)C=CC=CC=1.B.CSC>C1COCC1>[CH2:16]([O:15][C:12]1[CH:13]=[CH:14][C:5]([C@@H:3]([OH:4])[CH2:2][Br:1])=[C:6]2[C:11]=1[NH:10][C:9](=[O:23])[CH:8]=[CH:7]2)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 116678678-Benzyloxy-5-(2-bromoacetyl)-2-hydroxyquinolineHCID 12423031(Dimethyl sulfide)trihydroboron

Product 1

HCID 115308845-((1R)-2-bromo-1-hydroxyethyl)-8-phenylmethoxy-1H-quinolin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
1 °C

Procedure

A dry 5 liter flask equipped with a mechanical stirrer, thermometer, addition funnel and refluxing condenser was charged with 5-Bromoacetyl-8-benzyloxycarbostyril (100 gms/0.268 moles) and dry THF (1.2 liter) under argon. A solution of (R)-tetrahydro-1-methyl-3,3-diphenyl-(1H,3H)-pyrrolo[1,2-c][1,3,2]-oxazaborolidine catalyst in toluene (43 ml/0.388 moles) was added and reaction mass was chilled to 0-2° C. Then, 1M solution of borane-methyl sulfide (32.42 ml/0.3417 moles) in THF (342 ml) was added in 3 hours while maintaining temperature at 0-2° C. The reaction was stirred for another 15-20 minutes at same temperature. The reaction mass was quenched by addition of methanol (171 ml) in 15-20 minutes. The temperature of resulting solution was raised to 25-30° C. and concentrated to a volume of 500 ml under vacuum at 50° C. To this concentrate was added a mixture of water (1.45 liters) and concentrated HCl (74 ml) in 10-15 minutes. The resulting suspension was stirred for 30 minutes at 25° C. The solid 8-benzyloxy-5-[(R)-(2-bromo-1-hydroxyethyl)]-carbostyril obtained was isolated by filtration and washed with water till neutral pH, dried under vacuum at 60-65° C. for 12-14 hours. Yield-70-73 gms.

Workup

  1. customA dry 5 liter flask equipped with a mechanical stirrer
  2. additionthermometer, addition funnel
  3. temperaturerefluxing condenser
  4. customreaction mass
  5. temperaturewhile maintaining temperature at 0-2° C
  6. customThe reaction mass was quenched by addition of methanol (171 ml) in 15-20 minutes
  7. temperatureThe temperature of resulting solution was raised to 25-30° C.
  8. concentrationconcentrated to a volume of 500 ml under vacuum at 50° C
  9. additionTo this concentrate was added
  10. additiona mixture of water (1.45 liters) and concentrated HCl (74 ml) in 10-15 minutes
  11. stirringThe resulting suspension was stirred for 30 minutes at 25° C

Sources & evidence

ORD record
ord-99a51dc6b69147c2afe695444f1d64b9
Source dataset
uspto-grants-2012_08
Patent number
US08236959B2

Reaction notes

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