Formaldehyde → 2,2,2-trifluoro-1-(7-nitro-3,4-dihydroisoquinolin-2(1H)-yl)ethanone

HRID 1157560Notes

Reaction equation

HRID 1157560 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]([NH:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1)=[O:4].S(=O)(=O)(O)O.[CH2:24]=O>CC(O)=O>[N+:14]([C:11]1[CH:12]=[C:13]2[C:8]([CH2:7][CH2:6][N:5]([C:3](=[O:4])[C:2]([F:17])([F:18])[F:1])[CH2:24]2)=[CH:9][CH:10]=1)([O-:16])=[O:15]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 64237442,2,2-Trifluoro-N-[2-(4-nitro-phenyl)-ethyl]-acetamide

Product 1

HCID 219568152,2,2-trifluoro-1-(7-nitro-3,4-dihydroisoquinolin-2(1H)-yl)ethanoneYield 66%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

2,2,2-Trifluoro-N-[2-(4-nitrophenyl)ethyl]acetamide (21.9 g, 83.4 mmol) was dissolved in HOAc (80 mL) and sulfuric acid (120 mL) and paraformaldehyde (4.0 g, 125 mmol) were added at rt. The solution was stirred at rt for 24 h. The reaction was poured cautiously into approximately 1 L of ice with stirring. The resulting suspension of brown sludge was extracted into EtOAc. The organic was washed with saturated aqueous NaHCO3, brine and dried over MgSO4. The solvent was removed and the brown solid was triturated with hexanes. The brown solid was dried under vacuum and provided 15 g (66%) of the desired tetrahydroisoquinoline product. 1H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J=27.0 Hz, 1H), 8.05 (m, 1H), 7.47 (d, J=8.5 Hz, 1H), 4.88 (d, J=18.1 Hz, 2H), 3.81 (m, 2H), 3.06-2.97 (m, 2H).

Workup

  1. stirringwith stirring
  2. additionThe resulting suspension of brown sludge
  3. extractionwas extracted into EtOAc
  4. washThe organic was washed with saturated aqueous NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed
  7. customthe brown solid was triturated with hexanes
  8. customThe brown solid was dried under vacuum

Sources & evidence

ORD record
ord-9b0907e40a12476da0c18614095fcadb
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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