Trifluoroacetic acid → HCID 57804501, compound

HRID 2104439Notes

Reaction equation

HRID 2104439 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[CH2:11][N:10]([C:15](OC(C)(C)C)=O)[CH2:9][CH2:8]2)=[O:4].FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[CH2:11][N:10]([CH3:15])[CH2:9][CH2:8]2)=[O:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 114831762-tert-butyl 6-methyl 3,4-dihydroisoquinoline-2,6(1H)-dicarboxylate

Product 1

HCID 57804501HCID 57804501, compoundYield 66.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 3,4-dihydro(1H)isoquinoline-2,6-dicarboxylic acid 2-(tert-butyl) ester 6-methyl ester (WO00/09480) (344 mg) dissolved in methylene chloride (6 mL), under ice cooling, trifluoroacetic acid (3 mL) was added, followed by stirring for 30 minutes. The reaction mixture was concentrated, and diluted with chloroform. The resultant mixture was neutralized with saturated aqueous sodium hydrogencarbonate, followed by extracting with chloroform/methanol (4/1). The resultant organic layer was dried over sodium sulfate anhydrate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (chloroform:methanol=20:1→1:1), to thereby give 1, 2, 3, 4-tetrahydroisoquinoline-6-carboxylic acid methyl ester (154 mg). This material was dissolved in methylene chloride (5 mL), and formalin (90.6 μL) was added thereto at room temperate, followed by stirring for 10 minutes. Under ice cooling, acetic acid (46 μL) and sodium triacetoxyborohydride (269 mg) were added thereto. The mixture was stirred at room temperature for 105 minutes, and neutralized with saturated aqueous sodium hydrogencarbonate. The resultant mixture was extracted with chloroform. The organic layer was dried over sodium sulfate anhydrate, and concentrated under reduced pressure, to thereby give the title compound (162 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with chloroform
  3. extractionby extracting with chloroform/methanol (4/1)
  4. dry with materialThe resultant organic layer was dried over sodium sulfate anhydrate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (chloroform:methanol=20:1→1:1)
  7. dissolutionThis material was dissolved in methylene chloride (5 mL)
  8. additionformalin (90.6 μL) was added
  9. stirringby stirring for 10 minutes
  10. additionUnder ice cooling, acetic acid (46 μL) and sodium triacetoxyborohydride (269 mg) were added
  11. stirringThe mixture was stirred at room temperature for 105 minutes
  12. extractionThe resultant mixture was extracted with chloroform
  13. dry with materialThe organic layer was dried over sodium sulfate anhydrate
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6a6a79b7ad524d40b19b5680b1345f56
Source dataset
uspto-grants-2009_08
Patent number
US07576135B2

Reaction notes

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