Methyl 4-aminobenzoate → HCID 86761833, compound

HRID 2091399Notes

Reaction equation

HRID 2091399 reaction equation
[CH:1]1([C:6]([C:8]2[O:9][C:10]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:11]=3[C:12]=2[CH3:13])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1.C(=O)([O-])O.[Na+].C([BH3-])#N.[Na+]>O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl.C(O)(=O)C.ClCCl.C(N(CC)CC)C>[CH:1]1([CH:6]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:28][CH:29]=2)[C:8]2[O:9][C:10]3[CH:17]=[CH:16][C:15]([F:18])=[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 46941771HCID 46941771, compound

Product 1

HCID 86761833HCID 86761833, compoundYield 63.1%

Reagents, catalysts & solvents 5

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

Procedure

To a mixture of cyclopentyl(5-fluoro-3-methyl-1-benzofuran-2-yl)methanone (1.3 g) synthesized in Example A67(3), methyl 4-aminobenzoate (798 mg), triethylamine (5.88 mL) and dichloromethane (13 mL) was added titanium (IV) chloride (1.0M dichloromethane solution, 6.3 mL) at 0° C., and the mixture was stirred at room temperature for 2 hr under nitrogen atmosphere. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction. The solvent was concentrated under reduced pressure, 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 solid. To a solution of the obtained solid in tetrahydrofuran (20 mL) were added sodium cyanoborohydride (657 mg) and acetic acid (1.50 mL), and the mixture was stirred at room temperature for 16 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 subjected to silica gel column chromatography (hexane-ethyl acetate 90:10) to give the title compound (1.27 g, 63%) as a yellow amorphous compound.

Workup

  1. customto quench
  2. customthe reaction
  3. concentrationThe solvent was concentrated under reduced pressure
  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 solid
  9. stirringthe mixture was stirred at room temperature for 16 hr
  10. customto quench
  11. customthe reaction
  12. extractionthe 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

Sources & evidence

ORD record
ord-403c6c9f175d46d68a6feb579ecc593f
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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