Acetic Acid → HCID 9981094, compound

HRID 1791341Notes

Reaction equation

HRID 1791341 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH3:30])=[C:6]([C:8]([CH3:28])([CH3:27])[CH2:9][C:10](N)([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:11]([F:14])([F:13])[F:12])[CH:7]=1.C=O.[C:33](O)(=O)C.[C:37]([BH3-])#[N:38].[Na+]>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:29][CH3:30])=[C:6]([C:8]([CH3:28])([CH3:27])[CH2:9][C:10]([N:38]([CH3:37])[CH3:33])([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:11]([F:14])([F:13])[F:12])[CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 10319953HCID 10319953, compound

Product 1

HCID 9981094HCID 9981094, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-(5-Fluoro-2-methoxy-phenyl)-3-methyl-1-quinolin-4-ylmethyl-1-trifluoromethyl-butylamine (42.0 mg, 0.1 mmol) and the formaldehyde (1.49 ml, 20 mmol) in acetonitrile (2 ml) was stirred for 30 minutes at room temperature. The reaction mixture was acidified with acetic acid (57 μL, 1.0 mmol) and treated with sodium cyanoborohydride (31.4 mg, 0.5 mmol). The resulting mixture was stirred at room temperature for 15 h and quenched with NaHCO3 (sat. 2 ml). Phases were separated and the aqueous layer was extracted with CHCl3 (3×2ml). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The resulting oil was dissolved in Et2O and treated with HCl (2M in Ether) until the mixture was acidic (pH˜2). The ether layer was decanted and the salt was washed with ether (5×2 ml) and dried. The solid was dissolved in CHCl3, extracted with NaHCO3 (sat.), phases were separated and the aqueous layer was extracted with CHCl3 (2×4 ml). The combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified on SiO2 (20%–30%, EtOAc: Hexanes) to give 12.5 mg (28%) of the title compound.

Workup

  1. customquenched with NaHCO3 (sat. 2 ml)
  2. customPhases were separated
  3. extractionthe aqueous layer was extracted with CHCl3 (3×2ml)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting oil was dissolved in Et2O
  8. additiontreated with HCl (2M in Ether) until the mixture
  9. customThe ether layer was decanted
  10. washthe salt was washed with ether (5×2 ml)
  11. customdried
  12. dissolutionThe solid was dissolved in CHCl3
  13. extractionextracted with NaHCO3 (sat.), phases
  14. customwere separated
  15. extractionthe aqueous layer was extracted with CHCl3 (2×4 ml)
  16. dry with materialThe combined organic layers were dried over MgSO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customThe residue was purified on SiO2 (20%–30%, EtOAc: Hexanes)

Sources & evidence

ORD record
ord-27986a26fcae4b74a8276a0be92b4c2c
Source dataset
uspto-grants-2006_07
Patent number
US07074806B2

Reaction notes

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