Sodium hydride → 4-Ethoxycarbonyl-4-(3,5-difluorophenyl)-2-methyltetrahydropyran
Reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:7]=[C:8]([F:10])[CH:9]=1.I[CH2:18][CH:19]([CH3:24])[O:20][CH2:21][CH2:22]I>C1COCC1>[CH2:15]([O:14][C:12]([C:11]1([C:6]2[CH:5]=[C:4]([F:3])[CH:9]=[C:8]([F:10])[CH:7]=2)[CH2:22][CH2:21][O:20][CH:19]([CH3:24])[CH2:18]1)=[O:13])[CH3:16]Participants
Procedure
Sodium hydride (60% w/w dispersion in mineral oil, 9.17 g) was added portionwise to a solution of ethyl 3,5-difluorophenylacetate (17 g) in THF (400 ml) and the mixture was stirred at ambient temperature for 1 hour. A solution of 1,5-diiodo-2-methyl-3-oxapentane (30.3 g) in THF (20 ml) was added dropwise and the mixture was stirred at ambient temperature for 2 hours. The mixture was filtered and the filtrate was evaporated. The residue was purified by column chromatography using a 19:1 v/v mixture of petroleum ether (b.p. 40°-60° C.) and ethyl acetate as eluent. There was thus obtained, as a mixture of diastereoisomers, 4-ethoxycarbonyl-4-(3,5-difluorophenyl)-2-methyltetrahydropyran (16.5 g). The mixture of diastereoisomers was separated by further chromatography using a 10:1 v/v mixture of petroleum ether (b.p 40°-60° C.) and ethyl acetate as eluent. There was thus obtained:
Workup
- stirringthe mixture was stirred at ambient temperature for 2 hours
- filtrationThe mixture was filtered
- customthe filtrate was evaporated
- customThe residue was purified by column chromatography
- additiona 19:1 v/v mixture of petroleum ether (b.p. 40°-60° C.) and ethyl acetate as eluent
Sources & evidence
- ORD record
- ord-3751a7601dfd4238a982b21c088fa377
- Source dataset
- uspto-grants-1995_04
- Patent number
- US05407945
Reaction notes
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