Allyl iodide → 3-((S)-3-Allyl-6-cyclohexyl-2-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 579203Notes

Reaction equation

HRID 579203 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:23]#[C:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:8][C:9]=1[N:10]1[C:15](=[O:16])[CH2:14][CH2:13][CH2:12][C@H:11]1[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:4].[Li+].[CH3:30][CH:31]([N-]C(C)C)[CH3:32].ICC=C>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:23]#[C:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:8][C:9]=1[N:10]1[CH:11]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:12][CH2:13][C@@H:14]([CH2:32][CH:31]=[CH2:30])[C:15]1=[O:16])=[O:4]

Participants

5

Reactant 3

HCID 11166Allyl iodideHCID 2724682Lithium diisopropylamideHCID 666849233-((S)-2-Cyclohexyl-6-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 666846113-((S)-3-Allyl-6-cyclohexyl-2-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-((S)-2-cyclohexyl-6-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (200 mg, 0.5 mmol, 1.0 equiv) in THF (2.0 mL) was added LDA (2.0 M in THF, 0.3 mL, 0.6 mmol, 1.2 equiv) at −78° C. and the resulting solution was stirred at −78° C. for 10 minutes. To the solution was then added 3-iodo-propene (250 mg, 1.5 mmol, 3.0 equiv) and the reaction mixture was stirred at room temperature for 15 minutes. The reaction was quenched by addition of water. The mixture was extracted with EtOAc. The organic layer was washed with sat. NaHCO3 aq. solution and brine, dried over Na2SO4, and concentrated under vacuum. The residue was purified by silica gel column chromatography, Heptane/DCM (contained 3% EtOAc) to give 60 mg of less polar diastereomer and 100 mg of more polar diastereomer. MS: 442 [M+H+].

Workup

  1. customThe reaction was quenched by addition of water
  2. extractionThe mixture was extracted with EtOAc
  3. washThe organic layer was washed with sat. NaHCO3 aq. solution and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by silica gel column chromatography, Heptane/DCM (contained 3% EtOAc)
  7. customto give 60 mg of less polar diastereomer and 100 mg of more polar diastereomer

Sources & evidence

ORD record
ord-9f482f877f794e20a927cd087e018691
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

Loading…