Sodium hydride → HCID 67435148, compound

HRID 230710

Reaction equation

HRID 230710 reaction equation
Cl[C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7](O)=O.C(N1C=CN=C1)(N1C=CN=C1)=[O:11].[NH:22]1[CH2:26][CH2:25][CH2:24][C@H:23]1[CH2:27][OH:28].[H-].[Na+]>CN(C)C=O.O>[S:4]1[CH:3]2[CH2:7][N:22]3[CH:26]=[CH:25][CH:24]=[C:23]3[C:27](=[O:11])[O:28][C@H:2]2[CH2:6][CH2:5]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 640091L-ProlinolHCID 7012693-Chlorothiophene-2-carboxylic acid

Product 1

HCID 67435148HCID 67435148, compoundYield 11.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-chlorothiophene-2-carboxylic acid (0.5 g; 6.325 mmol) in dimethylformamide (5 ml) was added 1,1′-carbonyldiimidazole (1.07 g; 6.64 mmol) and the solution stirred at room temperature for 1 h, followed by the addition of (S)-(+)-2-pyrrolidinemethanol (0.655 ml; 6.64 mmol). The reaction was stirred at room temperature overnight whereupon 60% sodium hydride in mineral oil (0.507 g; 12.7 mmol) was carefully added and the mixture was heated slowly to 150° C. with the progress of the reaction being monitored by thin layer chromatography. The reaction was cautiously diluted with water and extracted with ethyl acetate and the organic layer washed with water then dried (Na2SO4) and evaporated to give the crude product. Purification by flash chromatography eluting with 0-10% (v/v) methanol in dichloromethane followed by crystallisation from ethyl acetate-petroleum ether (40-60) afforded the title compound (0.15 g). M.p.: 167-167.5° C.; EIMS: m/z=222.2 [M+H]+

Workup

  1. additionwas carefully added
  2. temperaturethe mixture was heated slowly to 150° C. with the progress of the reaction
  3. extractionextracted with ethyl acetate
  4. washthe organic layer washed with water
  5. dry with materialthen dried (Na2SO4)
  6. customevaporated
  7. customto give the crude product
  8. customPurification by flash chromatography
  9. washeluting with 0-10% (v/v) methanol in dichloromethane
  10. customfollowed by crystallisation from ethyl acetate-petroleum ether (40-60)

Sources & evidence

ORD record
ord-32173633450645a88c95458621e01b51
Source dataset
uspto-grants-2009_07
Patent number
US07566778B2

Linked notes

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