Citric Acid → HCID 57863356, compound

HRID 2075290Notes

Reaction equation

HRID 2075290 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:17]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:16]2[C:11]([CH:12]=[C:13]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[CH:14]=[N:15]2)=[C:10](I)[N:9]=1)=[O:7].[CH3:35]O.C(N(CC)CC)C.[C]=O.[C:46]([OH:58])(=[O:57])CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(OCC)(=O)C>[CH3:35][O:58][C:46]([C:10]1[C:11]2[CH:12]=[C:13]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[CH:14]=[N:15][C:16]=2[C:17]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:8]([C:6](=[O:7])[NH:5][CH2:4][CH2:3][O:2][CH3:1])[N:9]=1)=[O:57]

Participants

10

Reactant 5

HCID 311Citric AcidHCID 887MethanolHCID 8471TriethylamineHCID 59696213HCID 59696213, compoundHCID 178418416HCID 178418416, compound2×

Product 1

HCID 57863356HCID 57863356, compoundYield 84.1%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The above Compound 10 (400 mg, 0.7 mmol) and palladium acetate (8 mg, 0.035 mmol) were solved in dimethylformamide (11 ml), added with methanol (0.29 ml, 7.16 mmol) followed by triethylamine (0.30 ml, 2.15 mmol), and deaeration of the reaction vessel with carbon monoxide was repeated three times. Then the solution was stirred at room temperature in the presence of carbon monoxide. After 6 hours, the reaction mixture was added with ethyl acetate (40 ml), water (30 ml), an 10% citric acid (4 ml), and shaken for separation. Then the aqueous phase was extracted once with ethyl acetate, and the ethyl acetate phase was washed twice with water, dried over sodium sulfate and subjected to distillation under reduced pressure. The obtained residue (0.38 g) was subjected to silica gel chromatography, to give crystalline 8-benzyloxy-3-(4-fluorobenzyl)-7-(2-methoxyethylcarbamoyl)[1,6]naphthyridine-5-carboxylic acid methyl ester 11 (296 mg, 84.1%).

Workup

  1. extractionThen the aqueous phase was extracted once with ethyl acetate
  2. washthe ethyl acetate phase was washed twice with water
  3. dry with materialdried over sodium sulfate
  4. distillationsubjected to distillation under reduced pressure

Sources & evidence

ORD record
ord-df9b37185de44eb2bbe8e5a35eca566a
Source dataset
uspto-grants-2011_04
Patent number
US07919623B2

Reaction notes

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