Ammonium Chloride → 4-(3-Benzyloxy-5-fluorophenyl)-4-hydroxytetrahydropyran

HRID 1377592Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:10]=[C:11](Br)[CH:12]=[C:13]([F:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[O:22]1[CH2:27][CH2:26][C:25](=[O:28])[CH2:24][CH2:23]1.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:25]2([OH:28])[CH2:26][CH2:27][O:22][CH2:23][CH2:24]2)[CH:12]=[C:13]([F:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -75 °C

Procedure

A solution of 3-benzyloxy-1-bromo-5-fluorobenzene (29.1 g) in 250 ml of tetrahydrofuran was cooled to about -75° C. and n-butyl lithium (1.6M in hexane, 65 ml) was added dropwise.. The mixture was stirred at about -75° C. for about 1 hour and a solution of tetrahydropyran-4-one (10.4 g) was added dropwise. The mixture was stirred at about -75° C. for about 1 more hour then allowed to warm to about 0° C. A saturated aqueous solution of ammonium chloride was added and the tetrahydrofuran was evaporated in vacuo. The residue was partitioned between water and ethyl acetate. The organic phase was separated and dried over sodium sulfate. The residue was purified by column chromatography on silica gel eluting with methylene chloride/hexanes to give 9.2 g of the title compound as an oil.

Workup

stirringThe mixture was stirred at about -75° C. for about 1 more hour
temperatureto warm to about 0° C
customthe tetrahydrofuran was evaporated in vacuo
customThe residue was partitioned between water and ethyl acetate
customThe organic phase was separated
dry with materialdried over sodium sulfate
customThe residue was purified by column chromatography on silica gel eluting with methylene chloride/hexanes

Sources & evidence

ORD record: ord-1eb5ccf73b4d47a1b2b30a89ed689193
Source dataset: uspto-grants-1997_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05665749

Reaction notes

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