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

HRID 2091201Notes

Reaction equation

HRID 2091201 reaction equation
[CH:1]1([C:7]([C:9]2[O:10][C:11]3[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:12]=3[C:13]=2[CH3:14])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=1.C(=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C.C(Cl)Cl.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:31][CH:32]=2)[C:9]2[O:10][C:11]3[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:12]=3[C:13]=2[CH3:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

10

Reactant 4

HCID 12082Methyl 4-aminobenzoateHCID 516892Sodium Bicarbonate2×HCID 5003444Sodium cyanoborohydrideHCID 66777339Cyclohexyl(3-methyl-5-nitro-1-benzofuran-2-yl)methanone

Product 1

HCID 66778727Methyl 4-{[cyclohexyl(3-methyl-5-nitro-1-benzofuran-2-yl)methyl]amino}benzoateYield 61%

Reagents, catalysts & solvents 5

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

Procedure

To a mixture of cyclohexyl(3-methyl-5-nitro-1-benzofuran-2-yl)methanone (3.00 g) synthesized above, methyl 4-aminobenzoate (1.57 g), triethylamine (11.6 mL) and methylene chloride (40 mL) was added titanium (IV) chloride (1.37 mL), and the mixture was stirred overnight under argon atmosphere at room temperature. 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 to give a dark brown oil. To a solution (40 mL) of the obtained oil in tetrahydrofuran were added acetic acid (2.98 mL) and sodium cyanoborohydride (1.31 g), 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 (25% ethyl acetate/hexane) to give the title object compound (2.66 g, 61%) as an orange solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe reaction 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 oil
  8. stirringthe mixture was stirred at room temperature for 1 hr
  9. customto quench
  10. customthe reaction
  11. extractionthe reaction 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 (25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-8ac0b7c9ae4b4dcfae2783fe030b781c
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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