Lithium diisopropylamide → Methyl 3-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxy-1-oxobutyl]-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylate

HRID 240874Notes

Reaction equation

HRID 240874 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[C:9]([C:12]1[S:16][C:15]([C:17]([O-:19])=[O:18])=[C:14]2[CH2:20][CH2:21][CH2:22][CH2:23][C:13]=12)(=[O:11])[CH3:10].[Cl:24][C:25]1[CH:26]=[C:27]([C:32](=[O:37])[C:33]([F:36])([F:35])[F:34])[CH:28]=[C:29]([Cl:31])[CH:30]=1>C1COCC1>[Cl:24][C:25]1[CH:26]=[C:27]([C:32]([OH:37])([C:33]([F:34])([F:35])[F:36])[CH2:10][C:9]([C:12]2[S:16][C:15]([C:17]([O:19][CH3:2])=[O:18])=[C:14]3[CH2:20][CH2:21][CH2:22][CH2:23][C:13]=23)=[O:11])[CH:28]=[C:29]([Cl:31])[CH:30]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 27582311-(3,5-Dichlorophenyl)-2,2,2-trifluoroethan-1-oneHCID 86693745HCID 86693745, compound

Product 1

HCID 71014111Methyl 3-[3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxy-1-oxobutyl]-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylateYield 607.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add a solution of LDA (2M in THF, 19.5 mL, 3.89 mmol) to a suspension of 3-acetyl-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylate (7.4 g, 3.11 mmol) in dry THF (80 mL) at −78° C. under N2. After stirring for 1.5 h, add 1-(3,5-Dichloro-phenyl)-2,2,2-trifluoro-ethanone (9.9 g, 3.73 mmol) to the reaction mixture and stir the resultant mixture at the same temperature for additional 2 hours. Quench the reaction with saturated NH4Cl aqueous solution. Extract the aqueous mixture with EtOAc (100 mL×3). The combined organic layers are washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. Purify the residue by silica gel chromatograph (PE:EtOAc 50:1) to afford methyl 3-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxybutanoyl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylate as an orange solid (9.1 g, 60.4%). MS (m/z): 481 (M+1).

Workup

  1. customQuench
  2. customthe reaction with saturated NH4Cl aqueous solution
  3. extractionExtract the aqueous mixture with EtOAc (100 mL×3)
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under vacuum
  7. customPurify the residue by silica gel chromatograph (PE:EtOAc 50:1)

Sources & evidence

ORD record
ord-26f6811b2993461d975174f03d6a9aff
Source dataset
uspto-grants-2014_02
Patent number
US08648081B2

Reaction notes

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