Lithium diisopropylamide → (E)-2-Fluoro-3-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-but-2-enoic acid ethyl ester

HRID 1883267Notes

Reaction equation

HRID 1883267 reaction equation
[Li+].CC([N-]C(C)C)C.[CH3:9][CH2:10][O:11][C:12]([CH:14](P(OCC)(OCC)=O)[F:15])=[O:13].[CH3:24][C:25]1([CH3:44])[CH2:34][CH2:33][C:32]([CH3:36])([CH3:35])[C:31]2[CH:30]=[C:29]([C:37](=O)[CH3:38])[C:28]([O:40][CH2:41][CH2:42][CH3:43])=[CH:27][C:26]1=2>C1COCC1>[CH2:10]([O:11][C:12](=[O:13])/[C:14](/[F:15])=[C:37](\[C:29]1[C:28]([O:40][CH2:41][CH2:42][CH3:43])=[CH:27][C:26]2[C:25]([CH3:44])([CH3:24])[CH2:34][CH2:33][C:32]([CH3:35])([CH3:36])[C:31]=2[CH:30]=1)/[CH3:38])[CH3:9]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 2734865Triethyl 2-fluoro-2-phosphonoacetateHCID 101494431-(3-Propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)ethanone2×

Product 1

HCID 20740816(E)-2-Fluoro-3-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-but-2-enoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of LDA (12.1 mL, 2.0 M in heptane/THF/ethylbenzene) in THF (10 mL) at −78° C. was added triethyl 2-fluoro-2-phosphonoacetate (5.0 g, 20.7 mmol) in THF (10 mL). The reaction flask was removed from dry ice cooling bath for 12 min and then re-cooled to −78° C. 1-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone (Intermediate 5, 1.98 g, 6.89 mmol) in THF (10 mL) was added and the reaction was allowed to warm up to ambient temperature over night. The reaction was quenched with aqueous NH4Cl and extracted with Et2O (×3). The combined organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (3% EtOAc-hexane) to give a ˜10:1 mixture of the title compound and its 2-Z isomer (2.2 g). The mixture was used directly in the next reaction.

Workup

  1. customThe reaction flask was removed from dry ice cooling bath for 12 min
  2. temperatureto warm up to ambient temperature over night
  3. customThe reaction was quenched with aqueous NH4Cl
  4. extractionextracted with Et2O (×3)
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel (3% EtOAc-hexane)
  9. customto give

Sources & evidence

ORD record
ord-5d07e8b9e0234b318764687920829c6f
Source dataset
uspto-grants-2004_07
Patent number
US06759547B1

Reaction notes

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