Acetone → 6-bromo-4-(hydroxymethyl)-1-(4-methoxybenzyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one

HRID 1878013Notes

Reaction equation

HRID 1878013 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:9](=[O:20])[O:8][C:7]([C:23]([F:26])([F:25])[F:24])([CH:21]=C)[C:6]=2[CH:27]=1.[O:28]=[O+][O-].[BH4-].[Na+].CC(C)=O>ClCCl.CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:9](=[O:20])[O:8][C:7]([CH2:21][OH:28])([C:23]([F:26])([F:24])[F:25])[C:6]=2[CH:27]=1

Participants

7

Reactant 4

HCID 180AcetoneHCID 24823Ozone2×HCID 4311764Sodium borohydrideHCID 445498006-bromo-1-(4-methoxybenzyl)-4-(trifluoromethyl)-4-vinyl-1,4-dihydro-2H-3,1-benzoxazin-2-one

Product 1

HCID 445498016-bromo-4-(hydroxymethyl)-1-(4-methoxybenzyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

6-Bromo-1-(4-methoxybenzyl)-4-(trifluoromethyl)-4-vinyl-1,4-dihydro-2H-3,1-benzoxazin-2-one (71.5 g, 0.161 mol) was dissolved in dichloromethane (200 mL) and methanol (200 mL), and the solution was cooled to 0° C. and stirred in an ozone atmospher for 2 hours. After the ozone atmospher was replaced by a nitrogen atmospher, sodium borohydride (12.2 g, 0.323 mol) was slowly added thereto at 0° C. After the reaction solution was stirred at 0° C. for 10 minutes, excess acetone was added thereto. After the solvent was evaporated under reduced pressure, the resulting residue was diluted with ethyl acetate, and 1 N hydrochloric acid was added until the pH of the aqueous layer reached about 6. The organic layer was separated and washed with water and saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The resulting residue was crystallized from water and ethanol, whereby the objective compound (62.4 g, 87%) was obtained as a white solid.

Workup

  1. additionwas slowly added
  2. customat 0° C
  3. customAfter the solvent was evaporated under reduced pressure
  4. additionthe resulting residue was diluted with ethyl acetate, and 1 N hydrochloric acid
  5. additionwas added until the pH of the aqueous layer
  6. customThe organic layer was separated
  7. washwashed with water and saturated brine
  8. dry with materialdried over magnesium sulfate
  9. customAfter the drying agent was removed by filtration
  10. customthe solvent was evaporated under reduced pressure
  11. customThe resulting residue was crystallized from water and ethanol, whereby the objective compound (62.4 g, 87%)
  12. customwas obtained as a white solid

Sources & evidence

ORD record
ord-35e67e4acfec4bcab3d28e195e0a4a14
Source dataset
uspto-grants-2012_11
Patent number
US08314094B2

Reaction notes

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