Water → 4-(5-fluoro-3-(4-(2-methyl-1H-imidazol-1-yl)benzyloxy)phenyl)-4-methoxy-3,4,5,6-tetrahydro-2H-pyran

HRID 1291053Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([OH:16])[CH:5]=[C:6]([C:8]2([O:14][CH3:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.Cl.[CH3:18][C:19]1[N:20]([C:24]2[CH:31]=[CH:30][C:27]([CH2:28]Cl)=[CH:26][CH:25]=2)[CH:21]=[CH:22][N:23]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([O:16][CH2:28][C:27]2[CH:26]=[CH:25][C:24]([N:20]3[CH:21]=[CH:22][N:23]=[C:19]3[CH3:18])=[CH:31][CH:30]=2)[CH:5]=[C:6]([C:8]2([O:14][CH3:15])[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-(5-fluoro-3-hydroxyphenyl)-4-methoxy-3,4,5,6-tetrahydro-2H-pyran (1.4 g, 6.8 mmol), 4-(2-methylimidazol-1-yl)benzyl chloride hydrochloride (1.65 g, 6.8mmol) and potassium carbonate (7.2 g, 68 mmol) in dry DMF (10 ml) was stirred at 120° C. for 2 hours. The mixture was poured into water (100 ml) and extracted with ethyl acetate - benzene (300 ml, 2:1 v/v). The organic phase was washed with water (100 ml), brine (100 ml), dried (MgSO4) and evaporated. Purification of the residual yellow solids by column chromatograghy on silica gel (100 g) eluting with CH2Cl2 /methanol=10:1 and recrystallization from ethyl acetate-hexane gave 4-[5-fluoro-3-[4-(2-methylimidazol-1-yl)benzyloxy]phenyl]-4-methoxy-3,4,5,6-tetrahydro-2H-pyran (1.0 g, 39%) as off-white solids.

Workup

extractionextracted with ethyl acetate - benzene (300 ml, 2:1 v/v)
washThe organic phase was washed with water (100 ml), brine (100 ml)
dry with materialdried (MgSO4)
customevaporated
customPurification of the residual yellow solids by column chromatograghy on silica gel (100 g)
washeluting with CH2Cl2 /methanol=10:1 and recrystallization from ethyl acetate-hexane

Sources & evidence

ORD record: ord-5e170766a9ab421f8f85a925ee589b62
Source dataset: uspto-grants-1998_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05753682

Reaction notes

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