6-bromo-4-(phenylmethyl)-3,4-dihydro-2H-1,4-benzoxazine → (4-Benzyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-(5-bromo-2-isopropyl-phenyl)-methanol

HRID 1695870Notes

Reaction equation

HRID 1695870 reaction equation
[CH2:1]([N:8]1[C:13]2[CH:14]=[C:15](Br)[CH:16]=[CH:17][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[Br:24][C:25]1[CH:26]=[CH:27][C:28]([CH:33]([CH3:35])[CH3:34])=[C:29]([CH:32]=1)[CH:30]=[O:31]>C1COCC1>[CH2:1]([N:8]1[C:13]2[CH:14]=[C:15]([CH:30]([C:29]3[CH:32]=[C:25]([Br:24])[CH:26]=[CH:27][C:28]=3[CH:33]([CH3:35])[CH3:34])[OH:31])[CH:16]=[CH:17][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 583408326-bromo-4-(phenylmethyl)-3,4-dihydro-2H-1,4-benzoxazineHCID 583408355-Bromo-2-isopropylbenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 67117055(4-Benzyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-(5-bromo-2-isopropyl-phenyl)-methanolYield 58.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-Benzyl-6-bromo-3,4-dihydro-2H-benzo[1,4]oxazine (1.5 g, 4.93 mmol) in THF (20 mL) was added 1.6 M n-butyl lithium in hexanes (3.0 mL, 74.93 mmol) at −78° C. The reaction was stirred for 30 min. then transferred to a stirred solution of 5-bromo-2-isopropylbenzaldehyde (1.12 g, 4.93 mmol) in THF (15 mL) at −78° C. After stirring for 30 min, the reaction was quenched by the addition of saturated aqueous solution of ammonium chloride. The resulting mixture was extracted with ethyl acetate (3×30 mL), and the combined organic layers were washed with water (25 mL) and brine (25 mL), then dried over sodium sulfate, concentrated and purified using neutral alumina column chromatography to give (4-Benzyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-(5-bromo-2-isopropyl-phenyl)-methanol (1.3 g).

Workup

  1. stirringAfter stirring for 30 min
  2. customthe reaction was quenched by the addition of saturated aqueous solution of ammonium chloride
  3. extractionThe resulting mixture was extracted with ethyl acetate (3×30 mL)
  4. washthe combined organic layers were washed with water (25 mL) and brine (25 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified

Sources & evidence

ORD record
ord-e318dfffd70b4ba69060dd261cd6199d
Source dataset
uspto-grants-2012_04
Patent number
US08163704B2

Reaction notes

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