Hydrochloric Acid → HCID 18333146, compound

HRID 2269758Notes

Reaction equation

HRID 2269758 reaction equation
Cl.C([N:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]([CH:19]=[O:20])[CH:11]([CH2:21][N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:10]1)C1C=CC=CC=1>[Pd].CO>[CH:19]([N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[NH:9][CH2:10][CH:11]1[CH2:21][N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)=[O:20]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 18332939HCID 18332939, compound

Product 1

HCID 18333146HCID 18333146, compoundYield 98.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

10% Pd-C (200 mg) and concentrated hydrochloric acid (0.3 ml) were added to a methanol (25 ml) solution of 4-benzyl-1-formyl-2-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroquinoxaline (500 mg). The reaction mixture was subjected to catalytic hydrogenation at room temperature under 4.5 atmospheric pressure for 2 hours. The catalyst was removed by filtration, and the filtrate was concentrated. 10% Aqueous potassium carbonate solution was added to the residue, which was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, then dried and concentrated to give 1-formyl-2-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroquinoxaline (360 mg). Oxalyl chloride (0.19 ml) was added to a THF (5 ml) solution of 3-(4-biphenylyl)propionic acid (410 mg) under ice-cooling, to which was added DMF (one drop). The reaction mixture was stirred at room temperature for 30 minutes, which was concentrated. The residue was again dissolved in THF, which was concentrated. The residue was dissolved in THF (7 ml), which was added dropwise to a THF (7 ml) solution of 1-formyl-2-(pyrrolidin-1-yl)methyl-1,2,3,4-tetrahydroquinoxaline (360 mg) and triethylamine (0.31 ml) underice-cooling. The reaction mixture was stirred at the same temperature for one hour. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, then dried and concentrated. The residue was purified by alumina column chromatography (eluent: hexane to hexane/ethyl acetate=4/1), which was converted into its oxalate. The crystals were washed with IPE to give the entitled compound (350 mg).

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate was concentrated
  3. addition10% Aqueous potassium carbonate solution was added to the residue, which
  4. extractionwas extracted with ethyl acetate
  5. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  6. customdried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-64fad427ec4045d99cf0afa58807d9fc
Source dataset
uspto-grants-2001_12
Patent number
US06329389B1

Reaction notes

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