Formaldehyde → 1-(7-Chloro-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethan-1-one

HRID 1879645Notes

Reaction equation

HRID 1879645 reaction equation
S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][NH:15][C:16](=[O:21])[C:17]([F:20])([F:19])[F:18])=[CH:9][CH:8]=1.[CH2:22]=O>C(O)(=O)C>[Cl:6][C:7]1[CH:8]=[C:9]2[C:10]([CH2:13][CH2:14][N:15]([C:16](=[O:21])[C:17]([F:19])([F:20])[F:18])[CH2:22]2)=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 22292794n-Trifluoroacetyl-4-chlorophenethylamine

Product 1

HCID 574437351-(7-Chloro-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethan-1-oneYield 92.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a mixture of concentrated sulfuric acid (40 mL) and acetic acid (60 mL), N-[2-(4-chlorophenyl)ethyl]-2,2,2-trifluoroacetamide (14.2 g) and paraformaldehyde (2.79 g) were added sequentially and stirred overnight under an argon atmosphere. The reaction mixture was added to ice-cold water, extracted with ethyl acetate, and then washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to give 7-chloro-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline (13.7 g) as a light-yellow solid.

Workup

  1. additionwere added sequentially
  2. additionThe reaction mixture was added to ice-cold water
  3. extractionextracted with ethyl acetate
  4. washwashed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride
  5. dry with materialAfter drying over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-698ca425df4646fd8c3dc5e5e33ddc99
Source dataset
uspto-grants-2012_11
Patent number
US08318702B2

Reaction notes

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