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

HRID 1472736Notes

Reaction equation

HRID 1472736 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:20](=[O:23])[CH2:21][Br:22])=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C2(C3C=CC=CC=3)OB(C)N3CCC[C@H]23)C=CC=CC=1.C1(C)C=CC=CC=1>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:20]([OH:23])[CH2:21][Br:22])=[C:13]2[C:18]=1[NH:17][C:16](=[O:19])[CH:15]=[CH:14]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 116678678-Benzyloxy-5-(2-bromoacetyl)-2-hydroxyquinoline

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

8-(Benzyloxy)-5-(2-bromoacetyl)quinolin-2(1H)-one (26.0 g, 69.9 mmol) and (R)-3,3-diphenyl-1-methyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole (21.3 g, 76.8 mmol) were azeotroped with toluene (×3) then suspended in anhydrous THF (400 mL) under an atmosphere of nitrogen. The suspension was cooled to −20° C. (external temperature), and borane dimethyl sulfide complex solution (45.4 mL, 90.8 mmol, 2.0 M solution in THF) was added by syringe pump over 3 hours. After complete addition the reaction mixture was stirred for an hour before quenching with methanol (25 mL). The reaction was warmed to RT over 20 minutes. The mixture was concentrated in vacuo and the residue was suspended in aqueous hydrochloric acid (500 mL, 1 M solution) and stirred at RT for 18 hours. After this time, the solid was collected by filtration and washed with water (×3). The solid was partially dissolved in ethyl acetate and heated at reflux for 2 hours. The remaining solid was removed by hot filtration, and the filtrate was evaporated to afford the title compound. The solid collected from the hot ethyl acetate was again partially dissolved in ethyl acetate and heated at reflux for 2 hours then filtered to give filtrate containing pure product. This process was repeated four more times. The combined solid was recrystallised from ethyl acetate and petroleum ether to afford the title compound (20.0 g, 76%).

Workup

  1. additionwas added by syringe pump over 3 hours
  2. additionAfter complete addition the reaction mixture
  3. custombefore quenching with methanol (25 mL)
  4. concentrationThe mixture was concentrated in vacuo
  5. stirringstirred at RT for 18 hours
  6. filtrationAfter this time, the solid was collected by filtration
  7. washwashed with water (×3)
  8. dissolutionThe solid was partially dissolved in ethyl acetate
  9. temperatureheated
  10. temperatureat reflux for 2 hours
  11. customThe remaining solid was removed by hot filtration
  12. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-46356a7b14994436bb0282590891c535
Source dataset
uspto-grants-2015_04
Patent number
US09012644B2

Reaction notes

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