Methyl 4-aminobenzoate → Methyl 4-{[1-(5-methoxy-3-methyl-1-benzofuran-2-yl)-5-(methylsulfanyl)pentyl]amino}benzoate

HRID 2091234Notes

Reaction equation

HRID 2091234 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11](=O)[CH2:12][CH2:13][CH2:14][CH2:15][S:16][CH3:17])=[C:8]([CH3:19])[C:7]=2[CH:20]=1.[NH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1.C(=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>C(Cl)Cl.O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH:11]([NH:21][C:22]3[CH:23]=[CH:24][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:30][CH:31]=3)[CH2:12][CH2:13][CH2:14][CH2:15][S:16][CH3:17])=[C:8]([CH3:19])[C:7]=2[CH:20]=1

Participants

10

Reactant 4

HCID 12082Methyl 4-aminobenzoateHCID 516892Sodium Bicarbonate2×HCID 5003444Sodium cyanoborohydrideHCID 667773801-(5-Methoxy-3-methyl-1-benzofuran-2-yl)-5-(methylsulfanyl)pentan-1-one

Product 1

HCID 66777286Methyl 4-{[1-(5-methoxy-3-methyl-1-benzofuran-2-yl)-5-(methylsulfanyl)pentyl]amino}benzoateYield 67%

Reagents, catalysts & solvents 5

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

Procedure

To a mixture of 1-(5-methoxy-3-methyl-1-benzofuran-2-yl)-5-(methylsulfanyl)pentan-1-one (658 mg) synthesized above, methyl 4-aminobenzoate (375 mg), triethylamine (2.50 mL) and methylene chloride (10 mL) was added a 1.0M solution (2.70 mL) of titanium (IV) chloride in methylene chloride at 0° C., and the mixture was stirred under argon atmosphere at room temperature for 3.5 days. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, methylene chloride was evaporated in 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 solution (10 mL) of the obtained oil in tetrahydrofuran were added acetic acid (647 μL) and sodium cyanoborohydride (283 mg), and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction mixture 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 (0-50% ethyl acetate/hexane) to give the so title object compound (645 mg, 67%) as a brown oil.

Workup

  1. customto quench
  2. customthe reaction, methylene chloride
  3. customwas evaporated in 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 1 hr
  10. customto quench
  11. customthe reaction
  12. extractionthe reaction mixture was extracted with ethyl acetate
  13. washThe extract was washed with saturated brine
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel column chromatography (0-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f69cb5ebbefb4b2995c1b9b9238ba3a6
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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