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 1883267ノート

反応式

HRID 1883267 の反応式
[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]

参加物

5

反応物 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 回

生成物 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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-5d07e8b9e0234b318764687920829c6f
出典データセット
uspto-grants-2004_07
特許番号
US06759547B1

反応ノート

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