Citric Acid → HCID 67505370, compound

HRID 1929941Notes

Reaction equation

HRID 1929941 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][OH:30])=[N:10][CH:11]=[C:12]([CH:23]=2)[C:13]([NH:15][C@@H:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]2[OH:22])=[O:14])=[CH:4][CH:3]=1.C(=O)(O)[O-:32].[Na+].C(=O)([O-])[O-].[K+].[K+].ClN1C(=O)CCC1=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([OH:32])=[O:30])=[N:10][CH:11]=[C:12]([C:13](=[O:14])[NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[OH:22])[CH:23]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 31398ChlorosuccinimideHCID 516892Sodium BicarbonateHCID 67505621HCID 67505621, compound

Product 1

HCID 67505370HCID 67505370, compound

Reagents, catalysts & solvents 2

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

5-(4-Chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-6-(5-hydroxy-pentyloxy)-nicotinamide (0.23 g, 0.5 mmol) was dissolved in dichloromethane (15 mL). To the solution was added 2,2,6,6-tetramethyl-1-piperidinyloxy (1 mg), tetrabutylammoniumchlorid (1.5 mg), 5 mL of an aqueous solution of sodium bicarbonate (0.5 M) and potassium carbonate (0.05 M) and N-chlorosuccinimid (0.146 g, 1.1 mmol). The mixture was stirred for 72 h at room temperature and afterwards poured into citric acid (10%, 20 mL) and extracted with dichloromethane. Organic phases were pooled, dried with Na2SO4 and the solvent was evaporated. The residue (aldehyde contaminated with some starting alcohol) was redissolved in tent-butanol (5 mL). To the solution was added 2-methyl-butene solution (2 M in THF, 5 mL), sodium chlorite (210 mg), and sodium dihydrogenphosphate (0.345 g). The mixture was stirred for 72 h at room temperature and afterwards poured into citric acid (10%, 50 mL) and extracted with ethyl acetate. Organic phases were pooled, dried with MgSO4 and the solvent was evaporated. The residue was purified by column chromatography on silica (dichloromethane/methanol gradient) to yield 0.062 g of the title compound as a white foam, MS (ISP) 445.2 (M−H)+.

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialdried with Na2SO4
  3. customthe solvent was evaporated
  4. dissolutionwas redissolved in tent-butanol (5 mL)
  5. additionTo the solution was added 2-methyl-butene solution (2 M in THF, 5 mL), sodium chlorite (210 mg), and sodium dihydrogenphosphate (0.345 g)
  6. stirringThe mixture was stirred for 72 h at room temperature
  7. additionafterwards poured into citric acid (10%, 50 mL)
  8. extractionextracted with ethyl acetate
  9. dry with materialdried with MgSO4
  10. customthe solvent was evaporated
  11. customThe residue was purified by column chromatography on silica (dichloromethane/methanol gradient)

Sources & evidence

ORD record
ord-911b693973694f338d1fe4ed8cf9b794
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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