Formaldehyde → 2-Trifluoroacetyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline

HRID 969558Notes

Reaction equation

HRID 969558 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]([NH:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1)=[O:4].[CH2:20]=O.S(=O)(=O)(O)O>C(O)(=O)C>[F:1][C:2]([F:18])([F:19])[C:3]([N:5]1[CH2:6][CH2:7][C:8]2[C:13](=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[CH2:20]1)=[O:4]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 181764952,2,2-Trifluoro-N-{2-[4-(trifluoromethyl)phenyl]ethyl}acetamide

Product 1

HCID 181765382-Trifluoroacetyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinolineYield 98.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

2,2,2-Trifluoro-N-{2-[4-(trifluoromethyl)phenyl]ethyl}acetamide (4.00 g, 14 mmol) and paraformaldehyde (0.63 g) were combined in a flask and dissolved in acetic acid (11 mL). Sulfuric acid (11 mL) was added slowly. The mixture went from a cloudy solution to clear and an exothermic reaction was observed. After 40 min, the flask was lowered into an ice bath. The reaction was quenched with cold water and the resulting solution was extracted with EtOAc three times. The combined extracts were washed with water, saturated sodium bicarbonate and brine, dried (MgSO4), filtered, and concentrated to afford a yellow oil (4.1 g, 83%). MS calculated for C12H9F6NO: (M+H)+298; found 298.0.

Workup

  1. customan exothermic reaction
  2. customthe flask was lowered into an ice bath
  3. customThe reaction was quenched with cold water
  4. extractionthe resulting solution was extracted with EtOAc three times
  5. washThe combined extracts were washed with water, saturated sodium bicarbonate and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1b636174a7b047d980b288ccc181b87c
Source dataset
uspto-grants-2007_12
Patent number
US07307086B2

Reaction notes

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