Citric Acid → HCID 69414718, compound

HRID 853076Notes

Reaction equation

HRID 853076 reaction equation
[H-].[Na+].C(O[C:6]([C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][C:11]=2[O:17][C:18]([F:21])([F:20])[F:19])=[O:7])C.C(OC([N:29]1[CH2:33][C@H:32]([CH3:34])OS1(=O)=O)=O)(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[CH3:34][C@H:32]1[N:9]2[C:10]3[C:11]([O:17][C:18]([F:19])([F:20])[F:21])=[CH:12][CH:13]=[CH:14][C:15]=3[CH:16]=[C:8]2[C:6](=[O:7])[NH:29][CH2:33]1

Participants

7

Reactant 5

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 24758Sodium hydride2×HCID 11195739(s)-Tert-butyl 5-methyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide2×HCID 68889087HCID 68889087, compound

Product 1

HCID 69414718HCID 69414718, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (280mg of a 60% dispersion in mineral oil, 7 mmol) was added to a solution of 7-trifluoromethoxy-1H-indole-2-carboxylic acid ethyl ester (1.53 g, 5.6 mmol) and (S)-5-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester (1.53 g, 6.45 mmol) in N,N-dimethylformamide (15 mL) at 0° C. The solution was allowed to reach room temperature and stirred 36 h. Further amounts of sodium hydride (56 mg) and (S)-5-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester (306 mg) were added to complete the reaction. To the solution was added 10% aq. citric acid solution and the mixture stirred 1 h at room temperature. The organics were extracted with ethyl acetate (2×), the combined organic phases washed with sat. aq. NaHCO3 solution and brine, dried (Na2SO4), and evaporated. The residue was dissolved in dichloromethane (25 mL), cooled to 0° C. and treated with trifluoroacetic acid (12 mL). After removal of the ice bath, the solution was stirred for 30 min and evaporated under reduced pressure. The residue was taken up in methanol (20 mL) and K2CO3 (2.52 g, 19.5 mmol) added, and the mixture stirred 15 h at room temperature. The mixture was filtered, the filtrate diluted with ethyl acetate, washed with water, dried (Na2SO4) and evaporated. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate gradient) to afford the product as a pale yellow foam (89 mg, 64%). ISP-MS: m/e=285.1 (M++H).

Workup

  1. customto reach room temperature
  2. additionwere added
  3. customthe reaction
  4. stirringthe mixture stirred 1 h at room temperature
  5. extractionThe organics were extracted with ethyl acetate (2×)
  6. washthe combined organic phases washed with sat. aq. NaHCO3 solution and brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. dissolutionThe residue was dissolved in dichloromethane (25 mL)
  10. additiontreated with trifluoroacetic acid (12 mL)
  11. customAfter removal of the ice bath
  12. stirringthe solution was stirred for 30 min
  13. customevaporated under reduced pressure
  14. stirringthe mixture stirred 15 h at room temperature
  15. filtrationThe mixture was filtered
  16. additionthe filtrate diluted with ethyl acetate
  17. washwashed with water
  18. dry with materialdried (Na2SO4)
  19. customevaporated
  20. customThe residue was purified by column chromatography on silica gel (hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-ab069a7edd8e40d595d6febbe00c2e96
Source dataset
uspto-grants-2007_08
Patent number
US07253281B2

Reaction notes

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