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

HRID 1518615Notes

Reaction equation

HRID 1518615 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.CO>O1CCCC1>[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

4

Reactant 2

HCID 887MethanolHCID 116678678-Benzyloxy-5-(2-bromoacetyl)-2-hydroxyquinoline

Product 1

HCID 115308845-((1R)-2-bromo-1-hydroxyethyl)-8-phenylmethoxy-1H-quinolin-2-oneYield 74.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-50 °C

Procedure

Under an argon flow, 8-benzyloxy-5-(2-bromoacetyl)-1H-quinolin-2-one (374 g, 1.00 mol) was suspended in dehydrated tetrahydrofuran (3.8 L), CBS catalyst (27.8 g) was added thereto, and the mixture was stirred at −55 to −45° C. for 40 minutes. After adding dropwise a 0.9 M tetrahydrofuran solution of borane-tetrahydrofuran complex (1.27 L) at the same temperature, the reaction mixture was gradually warmed to 0° C. After adding methanol (1.3 L) dropwise, insoluble matter was removed by filtration and washed with tetrahydrofuran. The filtrate and the washing were mixed and concentrated under reduced pressure. To the residue was added purified water (6.3 L), and the mixture was stirred at room temperature overnight. The precipitate was collected by filtration and washed with purified water. Further, the precipitate was suspension-washed with ethyl acetate (4.8 L), collected by filtration, and dried under reduced pressure to obtain 8-benzyloxy-5-((R)-2-bromo-1-hyroxyethyl)-1H-quinolin-2-one (278 g). 1H-NMR (400 MHz, CDCl3) δ 9.26 (s, 1H), 8.08 (d, J=10.0 Hz, 1H), 7.37-7.45 (m, 5H), 7.28 (d, J=8.0 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 6.72 (d, J=10.0 Hz, 1H), 5.33 (dd, J=9.0 Hz, 4.0 Hz, 1H), 5.19 (s, 2H), 3.71-3.74 (m, 2H)

Workup

  1. temperaturethe reaction mixture was gradually warmed to 0° C
  2. custominsoluble matter was removed by filtration
  3. washwashed with tetrahydrofuran
  4. additionThe filtrate and the washing were mixed
  5. concentrationconcentrated under reduced pressure
  6. additionTo the residue was added
  7. custompurified water (6.3 L)
  8. stirringthe mixture was stirred at room temperature overnight
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with purified water
  11. washFurther, the precipitate was suspension-washed with ethyl acetate (4.8 L)
  12. filtrationcollected by filtration
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-2350ea4dab9e45a5b11b9d10f9f39324
Source dataset
uspto-grants-2015_07
Patent number
US09072734B2

Reaction notes

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