Methyl 4-aminobenzoate → Methyl 4-{[3-methyl-1-(3-methyl-1-benzofuran-2-yl)butyl]amino}benzoate

HRID 2091005Notes

Reaction equation

HRID 2091005 reaction equation
[CH3:1][CH:2]([CH3:16])[CH2:3][C:4]([C:6]1[O:7][C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]=1[CH3:11])=O.[NH2:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=1.C(=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>[Ti](Cl)(Cl)(Cl)Cl.O1CCCC1.CO.C(O)(=O)C.ClCCl.C(N(CC)CC)C>[CH3:1][CH:2]([CH3:16])[CH2:3][CH:4]([NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:26][CH:27]=1)[C:6]1[O:7][C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]=1[CH3:11]

Participants

11

Reactant 4

HCID 12082Methyl 4-aminobenzoateHCID 516892Sodium Bicarbonate2×HCID 5003444Sodium cyanoborohydrideHCID 667790263-Methyl-1-(3-methyl-1-benzofuran-2-yl)butan-1-one

Product 1

HCID 66777907Methyl 4-{[3-methyl-1-(3-methyl-1-benzofuran-2-yl)butyl]amino}benzoateYield 78.2%

Reagents, catalysts & solvents 6

HCID 24193Titanium TetrachlorideCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 3-methyl-1-(3-methyl-1-benzofuran-2-yl)butan-1-one (200 mg) synthesized above, methyl 4-aminobenzoate (140 mg), triethylamine (1.03 mL) and dichloromethane (5 mL) was added titanium (IV) chloride (122 μL) at 0° C., and the mixture was stirred at room temperature overnight. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the mixture 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 solid. To a mixture of the obtained solid, acetic acid (1 mL), methanol (5 mL) and tetrahydrofuran (5 mL) was added sodium cyanoborohydride (175 mg) by small portions, 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 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 (ethyl acetate:hexane=1:4, volume ratio) to give the title object compound (254 mg, 78%) as a pale-yellow solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a dark brown solid
  8. stirringthe mixture was stirred at room temperature for 1 hr
  9. customto quench
  10. customthe reaction
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe extract was washed with saturated brine
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio)

Sources & evidence

ORD record
ord-0aa6010598684d46ae3eba3a3c24b707
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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