Methyl chlorodifluoroacetate → 5,5-Dimethyl-3-trifluoromethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid methoxy-methyl-amide

HRID 1665951Notes

Reaction equation

HRID 1665951 reaction equation
[CH3:1][O:2][N:3]([CH3:18])[C:4]([C:6]1[S:7][C:8](I)=[C:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][C:10]=12)=[O:5].[F-:19].[K+].Cl[C:22]([F:28])([F:27])C(OC)=O>CN(C=O)C.[Cu]I>[CH3:1][O:2][N:3]([CH3:18])[C:4]([C:6]1[S:7][C:8]([C:22]([F:28])([F:19])[F:27])=[C:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][CH2:11][C:10]=12)=[O:5]

Participants

6

Reactant 3

HCID 73935Methyl chlorodifluoroacetateHCID 522689Potassium FluorideHCID 598608624,5,6,7-tetrahydro-3-iodo-N-methoxy-N,5,5-trimethyl-benzo[c]thiophene-1-carboxamide

Product 1

HCID 598608645,5-Dimethyl-3-trifluoromethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid methoxy-methyl-amideYield 92.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
134 °C

Procedure

3-Iodo-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid methoxy-methyl-amide (18 g, 47 mmol), CuI (14.5 g, 76 mmol) and KF (4.4 g, 76 mmol) are dissolved in DMF (80 mL). The solution is heated to 134° C. and methyl chlorodifluoroacetate (16.26 g, 113 mmol) is added via syringe pump over a period of 4 h. Gas evolution is observed. Upon complete addition, the mixture is cooled and poured into water/ice. The precipitate that forms is collected, suspended in DCM (600 mL), and filtered through a celite pad. The filtrate is washed with 0.5 N aq. HCl (250 mL), followed by sat. aq. NaHCO3 solution, dried over Na2SO4, filtered and evaporated to give 5,5-dimethyl-3-trifluoromethyl-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid methoxy-methyl-amide (14 g) as a brown oil; LC-MS: tR=1.10 min, [M+1]=322.20.

Workup

  1. additionUpon complete addition
  2. temperaturethe mixture is cooled
  3. customThe precipitate that forms is collected
  4. filtrationfiltered through a celite pad
  5. washThe filtrate is washed with 0.5 N aq. HCl (250 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-3071b8c1cc754b758093a7cb8b4516d8
Source dataset
uspto-grants-2011_10
Patent number
US08039644B2

Reaction notes

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