5-Bromo-2-chlorobenzaldehyde → (4-benzylspiro[3H-1,4-benzoxazine-2,1-cyclopropane]-6-yl)-(5-bromo-2-chloro-phenyl)methanol

HRID 1695842Notes

Reaction equation

HRID 1695842 reaction equation
[CH2:1]([N:8]1[C:15]2[CH:16]=[C:17](Br)[CH:18]=[CH:19][C:14]=2[O:13][C:10]2([CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[Br:26][C:27]1[CH:28]=[CH:29][C:30]([Cl:35])=[C:31]([CH:34]=1)[CH:32]=[O:33]>C1COCC1>[CH2:1]([N:8]1[C:15]2[CH:16]=[C:17]([CH:32]([C:31]3[CH:34]=[C:27]([Br:26])[CH:28]=[CH:29][C:30]=3[Cl:35])[OH:33])[CH:18]=[CH:19][C:14]=2[O:13][C:10]2([CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 106089255-Bromo-2-chlorobenzaldehydeHCID 583407784-benzyl-6-bromo-spiro[3H-1,4-benzoxazine-2,1-cyclopropane]HCID 178418339Butyllithium

Product 1

HCID 58340780(4-benzylspiro[3H-1,4-benzoxazine-2,1-cyclopropane]-6-yl)-(5-bromo-2-chloro-phenyl)methanolYield 49.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 4-benzyl-6-bromo-spiro[3H-1,4-benzoxazine-2,1′-cyclopropane] (1.12 g, 3.4 mmol) in THF (10 mL) was added 1.6 M solution of n-BuLi in hexanes (2.12 mL, 3.4 mmol) at −78° C. The reaction mixture was stirred for 30 min, and then transferred to a stirred solution of 5-bromo-2-chlorobenzaldehyde (745 mg, 3.4 mmol) in THF (10 mL) at −78° C. After stirring for 1 h, the reaction was quenched by the addition of saturated ammonium chloride solution and extracted with ethyl acetate. The ethyl acetate layer was washed with water, brine, dried over sodium sulphate, and concentrated. The resulting residue was purified by silica gel column chromatography to furnish (4-benzylspiro[3H-1,4-benzoxazine-2,1′-cyclopropane]-6-yl)-(5-bromo-2-chloro-phenyl)methanol (790 mg).

Workup

  1. stirringAfter stirring for 1 h
  2. customthe reaction was quenched by the addition of saturated ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with water, brine
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-34091c2304cc42dd864e9bc4df8f9fec
Source dataset
uspto-grants-2012_04
Patent number
US08163704B2

Reaction notes

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