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

HRID 2091078Notes

Reaction equation

HRID 2091078 reaction equation
[CH:1]1([C:6]([C:8]2[S:9][C:10]3[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=3[C:12]=2[CH3:13])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=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:6]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:27][CH:28]=2)[C:8]2[S:9][C:10]3[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=3[C:12]=2[CH3:13])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

10

Reactant 4

HCID 12082Methyl 4-aminobenzoateHCID 516892Sodium Bicarbonate2×HCID 5003444Sodium cyanoborohydrideHCID 66777325Cyclopentyl(3-methyl-1-benzothiophen-2-yl)methanone

Product 1

HCID 66778514Methyl 4-{[cyclopentyl(3-methyl-1-benzothiophen-2-yl)methyl]amino}benzoateYield 65.2%

Reagents, catalysts & solvents 5

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

Procedure

To a mixture of cyclopentyl(3-methyl-1-benzothiophen-2-yl)methanone (1.54 g) synthesized above, methyl 4-aminobenzoate (1.05 g), triethylamine (7.02 mL) and methylene chloride (30 mL) was added titanium (IV) chloride (829 μL), and the mixture was stirred under argon atmosphere at room temperature for 3 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 (30 mL) of the obtained oil in tetrahydrofuran were added acetic acid (721 μL) and sodium cyanoborohydride (792 mg), and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, the organic solvent 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. The residue was purified by silica gel column chromatography (0-30% ethyl acetate/hexane) to give the title object compound (1.56 g, 65%) as an orange solid.

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. customthe organic solvent was evaporated in 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-bbbcf00239c94e20b6fb7a4dc96c986d
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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