Triethyl 2-fluoro-2-phosphonoacetate → (2Z,4E,6E)-2,6-difluoro-3-methyl-7-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-octa-2,4,6-trienoic acid ethyl ester
Reaction equation
[CH3:1][CH2:2][O:3][C:4]([CH:6](P(OCC)(OCC)=O)[F:7])=[O:5].[Li]CCCC.[F:21]/[C:22](=[C:28](/[C:30]1[C:39]([O:40][CH2:41][CH2:42][CH3:43])=[CH:38][C:37]2[C:36]([CH3:45])([CH3:44])[CH2:35][CH2:34][C:33]([CH3:47])([CH3:46])[C:32]=2[CH:31]=1)\[CH3:29])/[CH:23]=[CH:24]/[C:25](=O)[CH3:26]>C1COCC1>[CH2:2]([O:3][C:4](=[O:5])/[C:6](/[F:7])=[C:25](\[CH3:26])/[CH:24]=[CH:23]/[C:22](/[F:21])=[C:28](\[C:30]1[C:39]([O:40][CH2:41][CH2:42][CH3:43])=[CH:38][C:37]2[C:36]([CH3:45])([CH3:44])[CH2:35][CH2:34][C:33]([CH3:47])([CH3:46])[C:32]=2[CH:31]=1)/[CH3:29])[CH3:1]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Following General Procedure B and using triethyl 2-fluoro-2-phosphonoacetate (0.3 mL, 1.44 mmol), THF (4 mL), n-BuLi (0.9 mL, 1.6 M in hexane, 1.44 mmol), (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 (Intermediate 9, 177 mg, 0.48 mmol) in THF (2 mL) at −78° C. for overnight, the title compound and its 2-E isomer were obtained by flash column chromatography on silica gel (3% EtOAc-hexane) as a ˜1.4:1 mixture (222 mg). Further purification by HPLC (2.5% EtOAc-hexane) afforded the title compound as a clear oil (102 mg, 47%).
Workup
- customat −78° C.
- customfor overnight
Sources & evidence
- ORD record
- ord-2d43b73bcb5748edb0042899e090b208
- Source dataset
- uspto-grants-2004_07
- Patent number
- US06759547B1
Reaction notes
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