Dimethylformamide → 3-[2-(4-Fluorophenyl)oxazol-4-ylmethoxy]cyclohexanol

HRID 1816370Notes

Reaction equation

[H-].[Na+].[CH:3]1([OH:10])[CH2:8][CH2:7][CH2:6][CH:5]([OH:9])[CH2:4]1.CN(C)C=O.Cl[CH2:17][C:18]1[N:19]=[C:20]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[O:21][CH:22]=1>O1CCCC1>[F:29][C:26]1[CH:25]=[CH:24][C:23]([C:20]2[O:21][CH:22]=[C:18]([CH2:17][O:9][CH:5]3[CH2:6][CH2:7][CH2:8][CH:3]([OH:10])[CH2:4]3)[N:19]=2)=[CH:28][CH:27]=1

Participants

Conditions

Temperature: 25 °C

Procedure

With ice-cooling, initially 2.25 g of an 80 percent suspension of sodium hydride and then 5.8 g of 1,3-cyclohexanediol were added to a mixture of 50 ml of dimethylformamide and 50 ml of tetrahydrofuran. The mixture was stirred at about 25° C. for 3 hours. 10.5 g of 4-chloromethyl-2-(4-fluorophenyl)oxazole (1) was then added, the mixture was heated at 70° C. and the reaction was monitored by thin-layer chromatography. After the reaction ended, the mixture was poured into ice-water and extracted with ethyl acetate. The organic phase was separated off, dried and concentrated and the residue was purified on silica gel by flash chromatography (ethyl acetate/n-heptane=1:1). This gave the alcohol 3 as an oil. C16H18FNO3 (291.33) MS(ESI): 292 (M+H+). Methyl 2-{3-[2-(4-fluorophenyl)oxazol-4-ylmethoxy]cyclohexyloxy}-6-methylbenzoate 5

Workup

temperatureWith ice-cooling
temperaturethe mixture was heated at 70° C.
extractionextracted with ethyl acetate
customThe organic phase was separated off
customdried
concentrationconcentrated
customthe residue was purified on silica gel by flash chromatography (ethyl acetate/n-heptane=1:1)

Sources & evidence

ORD record: ord-1e636681aacd4a868c7650c83c2aa127
Source dataset: uspto-grants-2005_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06884812B2

Reaction notes

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