Acetone → (3E, 5E)-5-Fluoro-6-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-hepta-3,5-dien-2-one
Reaction equation
[F:1]/[C:2](=[C:5](/[C:7]1[C:16]([O:17][CH2:18][CH2:19][CH3:20])=[CH:15][C:14]2[C:13]([CH3:22])([CH3:21])[CH2:12][CH2:11][C:10]([CH3:24])([CH3:23])[C:9]=2[CH:8]=1)\[CH3:6])/[CH:3]=O.[OH-].[Na+].[CH3:27][C:28]([CH3:30])=[O:29]>>[F:1]/[C:2](=[C:5](/[C:7]1[C:16]([O:17][CH2:18][CH2:19][CH3:20])=[CH:15][C:14]2[C:13]([CH3:22])([CH3:21])[CH2:12][CH2:11][C:10]([CH3:23])([CH3:24])[C:9]=2[CH:8]=1)\[CH3:6])/[CH:3]=[CH:27]/[C:28](=[O:29])[CH3:30]Participants
Procedure
To a solution of (E)-2-fluoro-3-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-but-2-enal (Intermediate 8, 208 mg, 0.63 mmol) in acetone (2 mL) was added 1M NaOH (2 mL) at 0° C. The mixture was stirred for 40 min, quenched with 2M H2SO4 (2 mL), and was stirred for 10 min. The mixture was then extracted with Et2O (×3). The combined organic layer was washed successively with brine, NaHCO3, brine, was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (5%→10%→20% EtOAc-hexane) to give the title compound (35 mg) and the intermediate β-hydroxy ketone (173 mg), which was converted to the title compound using catalytic para-tolunesulfonic acid (PTSA) in refluxing benzene.
Workup
- customquenched with 2M H2SO4 (2 mL)
- stirringwas stirred for 10 min
- extractionThe mixture was then extracted with Et2O (×3)
- washThe combined organic layer was washed successively with brine, NaHCO3, brine
- dry with materialwas dried over Na2SO4
- concentrationconcentrated in vacuo
- customThe residue was purified by flash column chromatography on silica gel (5%→10%→20% EtOAc-hexane)
Sources & evidence
- ORD record
- ord-776881a8398a40b492e6c0ea618d1185
- Source dataset
- uspto-grants-2004_07
- Patent number
- US06759547B1
Reaction notes
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