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

HRID 72593Notes

Reaction equation

HRID 72593 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-1095a317c9f94cce927d82697dbedff0
Source dataset
uspto-grants-2014_09
Patent number
US08828951B2

Reaction notes

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