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 1258864Notes

Reaction equation

HRID 1258864 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-df6e870207b4431e9ae6c64e69fc1225
Source dataset
uspto-grants-2013_06
Patent number
US08466114B2

Reaction notes

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