Citric Acid → HCID 137331190, compound

HRID 853109Notes

Reaction equation

HRID 853109 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]([O:14]CC)=O)[NH:9]2)=[CH:5][CH:4]=1.[H-].[Na+].C(OC([N:28]1[CH2:32][C@H:31]([CH:33]([C:38]([CH3:43])([CH3:42])[CH:39]([CH3:41])[CH3:40])[O:34][SiH:35]([CH3:37])[CH3:36])OS1(=O)=O)=O)(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.ClCCl>[CH3:37][SiH:35]([CH3:36])[O:34][CH:33]([C:38]([CH3:42])([CH3:43])[CH:39]([CH3:40])[CH3:41])[C@H:31]1[N:9]2[C:10]3[CH:11]=[C:3]([C:2]([F:1])([F:17])[F:18])[CH:4]=[CH:5][C:6]=3[CH:7]=[C:8]2[C:12](=[O:14])[NH:28][CH2:32]1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 22311001Ethyl 6-(trifluoromethyl)-1H-indole-2-carboxylateHCID 131724710HCID 131724710, compound

Product 1

HCID 137331190HCID 137331190, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.700 g ethyl 6-(trifluoromethyl)indole-2-carboxylate in 7 ml DMF was added 0.13 g sodium hydride 55% in oil and the mixture was stirred at room temperature for 30 min. To the resulting solution was added 1.30 g (R)-5-[Dimethyl-(1,1,2-trimethyl-propyl)-silanyloxymethyl]-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester and the mixture was stirred at room temperature for 18 h. The reaction mixture was distributed between 10% citric acid and dichloromethane and the organic phase was purified by chromatography on silica gel with dichloromethane. The product (1.15 g) was taken up in 11 ml TFA was stirred at 0° C. for 45 min. The solvent was evaporated and the residue was taken up in 10 ml methanol. To the resulting solution was added 1.00 g potassium carbonate and the mixture was stirred at room temperature for 3 h. The reaction mixture was purified by chromatography on silica gel with ethyl acetate to yield 0.36 g of the tiltle compound (m.p.: 143–144° C.) and 0.117 g of its desilylated analog (m.p.: 184–185° C.)

Workup

  1. stirringthe mixture was stirred at room temperature for 18 h
  2. customthe organic phase was purified by chromatography on silica gel with dichloromethane
  3. stirringwas stirred at 0° C. for 45 min
  4. customThe solvent was evaporated
  5. additionTo the resulting solution was added 1.00 g potassium carbonate
  6. stirringthe mixture was stirred at room temperature for 3 h
  7. customThe reaction mixture was purified by chromatography on silica gel with ethyl acetate

Sources & evidence

ORD record
ord-ec093717125d454f8ca95855fecc68fb
Source dataset
uspto-grants-2007_08
Patent number
US07253281B2

Reaction notes

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