Formaldehyde → HCID 131729393, compound

HRID 420795Notes

Reaction equation

HRID 420795 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][CH2:6][NH:7][C:8](=[O:13])[C:9]([F:12])([F:11])[F:10].C=O.OS(O)(=O)=O>CC(O)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][C:16]=1[Cl:17])[CH:8]=[N:7][CH2:6][CH2:5]2.[C:8]([NH2:7])([C:9]([F:12])([F:11])[F:10])=[O:13].[Cl:17][C:16]1[C:2]([Cl:1])=[C:3]2[C:4]([CH2:5][CH2:6][N:7]=[CH:8]2)=[CH:14][CH:15]=1.[C:8]([NH2:7])([C:9]([F:12])([F:11])[F:10])=[O:13]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 57692457HCID 57692457, compound

Product 2

HCID 131729393HCID 131729393, compoundYield 44%HCID 131729394HCID 131729394, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

N-(3,4-dichlorophenethyl)-2,2,2-trifluoroacetamide (2.860 g, 10.0 mmol) and paraformaldehyde (453 mg, 15.1 mmol) were placed in a round-bottom flask. A mixture composed of H2SO4 (20 mL) and AcOH (13 mL) was added at room temperature in one portion. The reaction mixture was stirred for 8 h at room temperature. The mixture was poured into ice-water (230 mL) and extracted with EtOAc (3×40 mL). The organic phases were combined, washed with water (25 mL), aqueous saturated NaHCO3 (25 mL), brine (25 mL), and then dried over sodium sulfate, filtered, and concentrated. The residue obtained was purified by silica gel column chromatography (gradient 1-45% EtOAc in hexanes, 120 g) providing 6,7-dichloro-3,4-dihydroisoquinoline-N-trifluoroacetamide (1.3 g, 44%) and 7,8-dichloro-3,4-dihydroisoquinoline-N-trifluoroacetamide (652 mg, 22%) as mixture of products (ratio was determined by NMR). LC/MS ((10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=298.3; tR=1.95 min.

Workup

  1. additionwas added at room temperature in one portion
  2. extractionextracted with EtOAc (3×40 mL)
  3. washwashed with water (25 mL), aqueous saturated NaHCO3 (25 mL), brine (25 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue obtained
  8. customwas purified by silica gel column chromatography (gradient 1-45% EtOAc in hexanes, 120 g)

Sources & evidence

ORD record
ord-0a13049ece034d39984dea4ca97485fd
Source dataset
uspto-grants-2012_01
Patent number
US08097636B2

Reaction notes

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