Hexane → 3-(3-Chlorophenyl)-alpha-(4-fluorophenyl)-2,1-benzisoxazole-5-methanol

HRID 1788039Notes

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.[F: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]([F: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 1.6M 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-fluorobenzaldehyde (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 taken up in diethyl ether and DIPE. The precipitate was filtered off, washed and dried, yielding 9.2 g (26.8%) of 3-(3-chlorophenyl)-α-(4-fluorophenyl)-2,1-benzisoxazole-5-methanol (intermediate 1), mp. 171° C.

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
filtrationThe precipitate was filtered off
washwashed
customdried

Sources & evidence

ORD record: ord-eee087fed59c4689a189d78aeef2b39e
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07511138B2

Reaction notes

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