Sodium hydride → HCID 67755178, compound

HRID 653580Notes

Reaction equation

HRID 653580 reaction equation
[NH2:1]/[C:2](/[C:9]([F:12])([F:11])[F:10])=[CH:3]\[C:4]([O:6]CC)=O.[H-].[Na+].[Cl:15][C:16]1[C:17]([N:27]=[C:28]=[O:29])=[C:18]([F:26])[S:19][C:20]=1[CH2:21][C:22]([O:24][CH3:25])=[O:23]>C1(C)C=CC=CC=1.CN(C)C=O>[Cl:15][C:16]1[C:17]([N:27]2[C:4](=[O:6])[CH:3]=[C:2]([C:9]([F:10])([F:11])[F:12])[NH:1][C:28]2=[O:29])=[C:18]([F:26])[S:19][C:20]=1[CH2:21][C:22]([O:24][CH3:25])=[O:23]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 5702529Ethyl 3-amino-4,4,4-trifluorocrotonateHCID 86745420HCID 86745420, compound

Product 1

HCID 67755178HCID 67755178, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
-30 °C

Procedure

A solution of 4.75 g of ethyl 3-amino-4,4,4-trifluorocrotonate in 50 ml of anhydrous toluene was added dropwise to a solution prepared by suspending 1.14 g of sodium hydride (purity: 55%) in 110 ml of dimethylformamide. Said dropwise addition was conducted at 0° C. under stirring over a period of 15 minutes. The resulting mixture was further stirred at 0° C. for 15 minutes. Then the reaction mixture was cooled to -30° C., and a solution of 6.9 g of 4-chloro-2-fluoro-5-methoxycarbonylmethylthiophenyl isocyanate in 50 ml of anhydrous toluene was added dropwise thereto. The resulting reaction mixture was returned to room temperature and stirred for 2 hours. After distilling off the solvent, the residual solution was added with ethyl acetate, washed twice with a solution of 20 ml of 2N hydrochloric acid and 500 ml of water, washed with a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate, and then ethyl acetate was distilled off to obtain a crude product. This crude product was preliminarily purified by silica gel column chromatography using CHCl3 as developing solvent and then purified by silica gel column chromatography using ethyl acetate/hexane (3:1) as developing solvent to obtain 1.5 g of the objective compound as viscous oil.

Workup

  1. customprepared
  2. additionaddition
  3. customwas conducted at 0° C.
  4. stirringThe resulting mixture was further stirred at 0° C. for 15 minutes
  5. customThe resulting reaction mixture
  6. customwas returned to room temperature
  7. stirringstirred for 2 hours
  8. distillationAfter distilling off the solvent
  9. additionthe residual solution was added with ethyl acetate
  10. washwashed twice with a solution of 20 ml of 2N hydrochloric acid and 500 ml of water
  11. washwashed with a saturated sodium chloride aqueous solution
  12. dry with materialdried over anhydrous sodium sulfate
  13. distillationethyl acetate was distilled off
  14. customto obtain a crude product
  15. customThis crude product was preliminarily purified by silica gel column chromatography
  16. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-7ef189d8e33647078cd4dc53c31219d0
Source dataset
uspto-grants-1992_07
Patent number
US05127935

Reaction notes

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