Acetyl chloride → 3-(1-Acetyl-piperidin-4-yl)-7-trifluoromethyl-benzo[b]thiophene-2-carboxylic acid methyl ester

HRID 501325Notes

Reaction equation

HRID 501325 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:9][C:8]2[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:11][CH:12]=[CH:13][C:7]=2[C:6]=1[CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)=[O:4].C(N(CC)CC)C.C1C[O:34][CH2:33][CH2:32]1.C(Cl)(=O)C>C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[S:9][C:8]2[C:10]([C:14]([F:16])([F:17])[F:15])=[CH:11][CH:12]=[CH:13][C:7]=2[C:6]=1[CH:18]1[CH2:23][CH2:22][N:21]([C:33](=[O:34])[CH3:32])[CH2:20][CH2:19]1)=[O:4]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 588176523-Piperidin-4-yl-7-trifluoromethyl-benzo[b]thiophene-2-carboxylic acid methyl ester

Product 1

HCID 588175743-(1-Acetyl-piperidin-4-yl)-7-trifluoromethyl-benzo[b]thiophene-2-carboxylic acid methyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a room temperature solution of 3-piperidin-4-yl-7-trifluoromethyl-benzo[b]thiophene-2-carboxylic acid methyl ester (4.37 g, 12.7 mmol), triethylamine (2.70 mL. 19.4 mmol), and anhydrous THF (80 mL) under nitrogen was added acetyl chloride (1.10 mL, 15.5 mmol) in one portion and the reaction stirred at room temperature overnight. The reaction was diluted with ethyl acetate (300 mL) and washed with water (150 mL) and brine (150 mL) successively. The organic layer was dried over magnesium sulfate, filtered, and the solvent removed. The residue was chromatographed on silica, eluting with 10% methanol/ethyl acetate, to afford 4.28 g (88%) of the desired product as a white solid, mp: 155.2° C.

Workup

  1. washwashed with water (150 mL) and brine (150 mL) successively
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent removed
  5. customThe residue was chromatographed on silica
  6. washeluting with 10% methanol/ethyl acetate

Sources & evidence

ORD record
ord-8f434184982e47a5867cf6b7a62d3572
Source dataset
uspto-grants-2010_08
Patent number
US07772252B2

Reaction notes

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