Thionyl Chloride → 3-Benzyloxy-1-(2,2-dimethoxyethyl)-5-hydroxymethyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide

HRID 1349501Notes

Reaction equation

HRID 1349501 reaction equation
[CH2:1]([O:8][C:9]1[C:10](=[O:35])[C:11]([C:32](O)=[O:33])=[CH:12][N:13]([CH2:26][CH:27]([O:30][CH3:31])[O:28][CH3:29])[C:14]=1[C:15](=[O:25])[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1.S([O-])(O)(=O)=O.[K+]>O1CCCC1.C(N(CC)CC)C>[Cl:24][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][CH:21]=1)[CH2:17][NH:16][C:15]([C:14]1[N:13]([CH2:26][CH:27]([O:28][CH3:29])[O:30][CH3:31])[CH:12]=[C:11]([CH2:32][OH:33])[C:10](=[O:35])[C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:25]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 516920Potassium bisulfateHCID 230776405-Benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acidHCID 68718528lithium aluminium hydride THF

Product 1

HCID 588591753-Benzyloxy-1-(2,2-dimethoxyethyl)-5-hydroxymethyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamideYield 47.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

5-Benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (517 mg) obtained in Example 161, Step 4 and triethylamine (0.43 ml) were added to tetrahydrofuran (7 ml), and thionyl chloride (0.098 ml) was subsequently added at 0° C. The mixture was stirred at room temperature for 3 min and the reaction mixture was cooled to −78° C. 1M Lithium aluminum hydride/tetrahydrofuran solution (1.55 ml) was added dropwise. After stirring at the same temperature for 3 min, 5% aqueous potassium hydrogen sulfate solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried, concentrated and purified by silica gel column chromatography (ethyl acetate-ethyl acetate:methanol=20:1) to give 3-benzyloxy-1-(2,2-dimethoxyethyl)-5-hydroxymethyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid 3-chlorobenzylamide (240 mg).

Workup

  1. additionwas subsequently added at 0° C
  2. temperaturethe reaction mixture was cooled to −78° C
  3. stirringAfter stirring at the same temperature for 3 min
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe ethyl acetate layer was dried
  6. concentrationconcentrated
  7. custompurified by silica gel column chromatography (ethyl acetate-ethyl acetate:methanol=20:1)

Sources & evidence

ORD record
ord-ab3e690a2a294fa7b541457ec8d9b959
Source dataset
uspto-grants-2007_05
Patent number
US07211572B2

Reaction notes

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