Citric Acid → HCID 58508951, compound

HRID 454674Notes

Reaction equation

HRID 454674 reaction equation
[OH-].[Na+].[OH:3][C:4]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[CH:27][C:5]=1[C:6]([NH:8][C:9]1[CH:21]=[C:20]([C:22]2[S:23][CH:24]=[CH:25][CH:26]=2)[CH:19]=[CH:18][C:10]=1[C:11]([O:13]C(C)(C)C)=[O:12])=[O:7].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.O>O1CCOCC1.CO.C(OCC)(=O)C>[OH:3][C:4]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]2)=[CH:27][C:5]=1[C:6]([NH:8][C:9]1[CH:21]=[C:20]([C:22]2[S:23][CH:24]=[CH:25][CH:26]=2)[CH:19]=[CH:18][C:10]=1[C:11]([OH:13])=[O:12])=[O:7]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 962WaterHCID 14798Sodium Hydroxide4×HCID 58508527HCID 58508527, compound

Product 1

HCID 58508951HCID 58508951, compoundYield 46.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
52.5 °C

Procedure

A 1 mol/L aqueous solution of sodium hydroxide (0.17 mL) was added to a solution mixture of the obtained tert-butyl 2-(2-hydroxy-5-(piperidin-1-yl)benzamido)-4-(thiophen-2-yl)benzoate (0.027 g) in dioxane (2.0 mL) and methanol (2.0 mL), followed by stirring at 50 to 55° C. for 1 hour. The reaction mixture was cooled to room temperature, and a 1 mol/L aqueous solution of sodium hydroxide (0.11 mL) was added thereto, followed by stirring at 50 to 55° C. for 2 hours. The reaction mixture was cooled to room temperature, and a 1 mol/L aqueous solution of sodium hydroxide (0.056 mL) was added thereto, followed by stirring at 55° C. for 1 hour. The reaction mixture was cooled to room temperature, and a 1 mol/L aqueous solution of sodium hydroxide (0.056 mL) was added thereto, followed by stirring at 60° C. for 2 hours. The reaction mixture was cooled to room temperature and then adjusted to a pH of 7.7 with a 10% aqueous solution of citric acid, and water and ethyl acetate were added thereto. The organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, and the resulting mixture was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 100-80% chloroform/methanol] to obtain 0.011 g of 2-(2-hydroxy-5-(piperidin-1-yl)benzamido)-4-(thiophen-2-yl)benzoic acid as an orange solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringby stirring at 50 to 55° C. for 2 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. stirringby stirring at 55° C. for 1 hour
  5. temperatureThe reaction mixture was cooled to room temperature
  6. stirringby stirring at 60° C. for 2 hours
  7. temperatureThe reaction mixture was cooled to room temperature
  8. additionwere added
  9. customThe organic layer was separated
  10. extractionthe aqueous layer was extracted with chloroform
  11. dry with materialthe resulting mixture was dried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography [eluent: 100-80% chloroform/methanol]

Sources & evidence

ORD record
ord-0a78f42b42fd4c3485dcf4263de32c6e
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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