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

HRID 1878015Notes

Reaction equation

HRID 1878015 reaction equation
C1COCC1.O.[N:7]([CH2:10][C:11]1([C:32]([F:35])([F:34])[F:33])[C:16]2[CH:17]=[C:18]([Br:21])[CH:19]=[CH:20][C:15]=2[N:14]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:13](=[O:31])[O:12]1)=[N+]=[N-].P(OC)(OC)OC>C(OCC)(=O)C>[NH2:7][CH2:10][C:11]1([C:32]([F:34])([F:35])[F:33])[C:16]2[CH:17]=[C:18]([Br:21])[CH:19]=[CH:20][C:15]=2[N:14]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:13](=[O:31])[O:12]1

Participants

6

Reactant 4

HCID 962Water2×HCID 8028TetrahydrofuranHCID 8472Trimethyl phosphiteHCID 445498024-(azidomethyl)-6-bromo-1-(4-methoxybenzyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one

Product 1

HCID 445498034-(aminomethyl)-6-bromo-1-(4-methoxybenzyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixed solution of THF (130 mL) and water (65 mL) containing 4-(azidomethyl)-6-bromo-1-(4-methoxybenzyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one (46 g, 98.0 mmol), trimethyl phosphite (23.1 mL, 195 mmol) was added at room temperature, and the reaction solution was stirred overnight at 60° C. After the reaction solution was left to cool, water was added thereto, and the resulting solution was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. To the residue, a 4 N hydrochloric acid-dioxane solution (200 mL) was added, and the mixture was stirred at room temperature for 24 hours. After the solvent was removed under reduced pressure, the residue was diluted with ethyl acetate, which was washed sequentially with a 2 N aqueous sodium hydroxide solution and saturated brine and the organic layer was dried over magnesium sulfate, whereby the objective compound (30.9 g, 71%) was obtained as a white solid.

Workup

  1. additionwas added at room temperature
  2. waitAfter the reaction solution was left
  3. temperatureto cool
  4. customthe organic layer was separated
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. customAfter the drying agent was removed by filtration
  8. customthe solvent was evaporated under reduced pressure
  9. additionTo the residue, a 4 N hydrochloric acid-dioxane solution (200 mL) was added
  10. stirringthe mixture was stirred at room temperature for 24 hours
  11. customAfter the solvent was removed under reduced pressure
  12. additionthe residue was diluted with ethyl acetate, which
  13. washwas washed sequentially with a 2 N aqueous sodium hydroxide solution and saturated brine
  14. dry with materialthe organic layer was dried over magnesium sulfate, whereby the objective compound (30.9 g, 71%)
  15. customwas obtained as a white solid

Sources & evidence

ORD record
ord-cfa160c17b734c67b5a2c8bb74cb768c
Source dataset
uspto-grants-2012_11
Patent number
US08314094B2

Reaction notes

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