Sodium Bicarbonate → HCID 66777011, compound

HRID 2091055Notes

Reaction equation

HRID 2091055 reaction equation
[CH:1]1([C:7]([C:9]2[O:10][C:11]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:12]=3[C:13]=2[CH3:14])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:20][C:21]1[N:26]=[CH:25][C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:22]=1.C(=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C.O1CCCC1.C(O)C.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:20][C:21]2[N:26]=[CH:25][C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:22]=2)[C:9]2[O:10][C:11]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:12]=3[C:13]=2[CH3:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

11

Reactant 4

HCID 516892Sodium Bicarbonate2×HCID 737487Methyl 6-aminonicotinateHCID 5003444Sodium cyanoborohydrideHCID 66777466HCID 66777466, compound

Product 1

HCID 66777011HCID 66777011, compoundYield 12%

Reagents, catalysts & solvents 6

HCID 24193Titanium TetrachlorideCatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of cyclohexyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methanone (3.00 g) synthesized above, methyl 6-aminopyridine-3-carboxylate (1.93 g), triethylamine (12.8 mL) and methylene chloride (40 mL) was added a 1.0M solution (13.8 mL) of titanium (IV) chloride in methylene chloride at 0° C., and the mixture was stirred under an argon atmosphere at room temperature for 1.5 days. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, methylene chloride was removed by an evaporator, and the residue was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a dark brown oil. To a mixture of the obtained oil, ethanol (40 mL) and tetrahydrofuran (20 mL) were added acetic acid (3.29 mL) and sodium cyanoborohydride (3.61 g), and the mixture was stirred at room temperature for 3 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, the organic solvent was removed by an evaporator, and the residue was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-30% ethyl acetate/hexane) to give the title object compound (547 mg, 12%) as a pale-brown solid.

Workup

  1. customto quench
  2. customthe reaction, methylene chloride
  3. customwas removed by an evaporator
  4. extractionthe residue was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto give a dark brown oil
  9. stirringthe mixture was stirred at room temperature for 3 hr
  10. customto quench
  11. customthe reaction
  12. customthe organic solvent was removed by an evaporator
  13. extractionthe residue was extracted with ethyl acetate
  14. washThe extract was washed with saturated brine
  15. dry with materialdried over magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (0-30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0bbf793aba7e4245a556ef1a9e02c37d
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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