4-Methylbenzaldehyde → 3-(3-Chlorophenyl)-alpha-(4-methylphenyl)-2,1-benzisoxazole-5-methanol

HRID 1788056Notes

Reaction equation

[Li]CCCC.CCCCCC.Br[C:13]1[CH:14]=[CH:15][C:16]2[C:17]([CH:28]=1)=[C:18]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=1)[O:19][N:20]=2.[CH3:29][C:30]1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[CH:32][CH:31]=1>C1COCC1>[Cl:27][C:23]1[CH:22]=[C:21]([C:18]2[O:19][N:20]=[C:16]3[CH:15]=[CH:14][C:13]([CH:34]([C:33]4[CH:36]=[CH:37][C:30]([CH3:29])=[CH:31][CH:32]=4)[OH:35])=[CH:28][C:17]=23)[CH:26]=[CH:25][CH:24]=1

Participants

Conditions

Temperature: -70 °C

Procedure

nBuLi 1.6 M in hexane (0.112 mol) was added dropwise at −70° C. under N2 flow to a mixture of 5-bromo-3-(3-chlorophenyl)-2,1-benzisoxazole (0.097 mol) in THF (300 ml). The mixture was stirred at −70° C. for 15 min. A mixture of 4-methylbenzaldehyde (0.112 mol) in THF (100 ml) was added dropwise. The mixture was stirred at −70° C. for 30 min, then hydrolized and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue was purified by column chromatography over silica gel (20-45 μm) (eluent: DCM/EtOAc 96/4). The pure fractions were collected and the solvent was evaporated, yielding 13 g (38.3%) of 3-(3-chlorophenyl)-α-(4-methylphenyl)-2,1-benzisoxazole-5-methanol (intermediate 18).

Workup

additionwas added dropwise
stirringThe mixture was stirred at −70° C. for 30 min
extractionhydrolized and extracted with EtOAc
customThe organic layer was separated
dry with materialdried (MgSO4)
filtrationfiltered
customthe solvent was evaporated till dryness
customThe residue was purified by column chromatography over silica gel (20-45 μm) (eluent: DCM/EtOAc 96/4)
customThe pure fractions were collected
customthe solvent was evaporated

Sources & evidence

ORD record: ord-da903ade3be946ffa0911b31ee60f241
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07511138B2

Reaction notes

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