Sodium hydride → HCID 59702049, compound

HRID 902517Notes

Reaction equation

HRID 902517 reaction equation
[H-].[Na+].CO[C:5]([C:7]1[S:8][CH:9]=[C:10](C)[C:11]=1[NH:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)=[O:6].C([CH:25]([C:29](Cl)=[O:30])[C:26](Cl)=[O:27])C.[O-:32][CH2:33][CH3:34].[Na+]>CN(C=O)C>[CH2:33]([O:32][C:29]([C:25]1[C:26](=[O:27])[N:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)[C:11]2[CH:10]=[CH:9][S:8][C:7]=2[C:5]=1[OH:6])=[O:30])[CH3:34]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 2723922Sodium ethoxideHCID 109209242-Ethylpropanedioyl dichlorideHCID 69316970HCID 69316970, compound

Product 1

HCID 59702049HCID 59702049, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Solid NaH (60% in min. oil, 4.62 g, 135 mmol) was added in portions to a stirred solution of 3-(4-methoxybenzylamino)-thiophene-2-carboxylic acid methyl ester (53) (26.69 g, 96 mmol) in dry DMF. The solution was stirred for 10 min. at room temperature and cooled to 0° C. Ethyl malonyl chloride was added slowly and the solution was further stirred at room temperature for 15 min. Sodium ethoxide (13.1 g, 192 mmol) was added to the solution and the solution was heated to 110° C. for 2 h. The solution was cooled and excess solvent was distilled off The residue was dissolved in a mixture of water (350 mL) and 4 M NaOH (50 mL), and the insoluble impurities were filtered off The filtrate was washed by diisopropyl ether and then acidified to pH 4 by cold diluted HCl solution. The solids formed were filtered, washed by water, and dried under vacuum at room temperature to yield 27 g (79%) of 7-hydroxy-4-(4-methoxybenzyl)-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester as off-white solids. 1H NMR (400 MHz, DMSO-d6) δ 1.30 (t, J=7.2 Hz, 3H), 3.70 (s, 3H), 4.32 (q, J=7.2 Hz, 2H), 5.27 (s, 2H), 6.86 (d, J=8.8 Hz, 2H), 7.21 (d, J=8.8 Hz, 2H), 7.34 (d, J=5.6 Hz, 1H), 8.14 (d, J=5.6 Hz, 1H), 13.31 (br, 1H) ppm; MS m/z=360 amu (M++1).

Workup

  1. temperaturecooled to 0° C
  2. stirringthe solution was further stirred at room temperature for 15 min
  3. temperaturethe solution was heated to 110° C. for 2 h
  4. temperatureThe solution was cooled
  5. distillationexcess solvent was distilled off The residue
  6. dissolutionwas dissolved in a mixture of water (350 mL) and 4 M NaOH (50 mL)
  7. filtrationthe insoluble impurities were filtered off The filtrate
  8. washwas washed by diisopropyl ether
  9. customThe solids formed
  10. filtrationwere filtered
  11. washwashed by water
  12. customdried under vacuum at room temperature

Sources & evidence

ORD record
ord-cd54862c82cb4c5886c7ef5073bde605
Source dataset
uspto-grants-2008_04
Patent number
US07365200B2

Reaction notes

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