Lithium diisopropylamide → HCID 66880829, compound

HRID 2242061Notes

Reaction equation

HRID 2242061 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1)=[O:10].C([N-]C(C)C)(C)C.[Li+].[CH2:30]([C:34]1[CH:39]=[CH:38][C:37]([C@H:40]([CH3:44])[C:41](Cl)=[O:42])=[CH:36][CH:35]=1)[CH:31]([CH3:33])[CH3:32]>O1CCCC1>[Cl:21][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[CH:8]=[C:9]([O:10][C:41](=[O:42])[C@H:40]([C:37]1[CH:38]=[CH:39][C:34]([CH2:30][CH:31]([CH3:33])[CH3:32])=[CH:35][CH:36]=1)[CH3:44])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 10609225(αS)-α-Methyl-4-(2-methylpropyl)benzeneacetyl chlorideHCID 668811982-(3,5-Dichloro-pyridin-4-yl)-1-(3,4-dimethoxy-phenyl)-ethanone

Product 1

HCID 66880829HCID 66880829, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 2-(3,5-dichloro-pyridin-4-yl)-1-(3,4-dimethoxy -phenyl)-ethanone (2.0 g, 6.2 mmol) in dry tetrahydrofuran (10 ml) was cooled down to −78° C. then a 1.8 M solution of lithium diisopropylamide in tetrahydrofuran (4.1 ml, 7.4 mmol) was added dropwise keeping the temperature below −70° C. The resulting solution was stirred for 30 min., then added with a solution of 2-(S)-(4-isobutyl-phenyl)-propionyl chloride (1.4 g, 6.4 mmol) in dry tetrahydrofuran (10 ml) and left to warm to room temperature. After stirring for further 30 min., the reaction was quenched with brine (20 ml) and water (50 ml) and the mixture was extracted with ethyl acetate (2×40 ml). The combined organic layers were dried over sodium sulphate and evaporated under reduced pressure to give an oil as mixture of Z and E isomers. These were separated by preparative HPLC water (water/acetonitrile=70/30 to 20/80).

Workup

  1. customthe temperature below −70° C
  2. waitleft
  3. stirringAfter stirring for further 30 min.
  4. customthe reaction was quenched with brine (20 ml) and water (50 ml)
  5. extractionthe mixture was extracted with ethyl acetate (2×40 ml)
  6. dry with materialThe combined organic layers were dried over sodium sulphate
  7. customevaporated under reduced pressure
  8. customto give an oil
  9. additionas mixture of Z and E isomers
  10. customThese were separated by preparative HPLC water (water/acetonitrile=70/30 to 20/80)

Sources & evidence

ORD record
ord-be5dfef5ea1d47c1ad0a5994bf1aab83
Source dataset
uspto-grants-2010_03
Patent number
US07671066B2

Reaction notes

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