Citric Acid → HCID 69911076, compound

HRID 353396Notes

Reaction equation

HRID 353396 reaction equation
CC(C)([O-])C.[K+].O[CH:8](S([O-])(=O)=O)[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:13]([CH3:23])[CH:12]=1.[Na+:28].[C:29]([O:33][C:34](=[O:48])[CH2:35][CH:36](P(OCC)(OCC)=O)[C:37]([OH:39])=[O:38])([CH3:32])([CH3:31])[CH3:30].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[OH-].[Na+].C(=O)(O)[O-].[Na+]>C1COCC1.C(O)(C)(C)C.O>[Na+:28].[C:29]([O:33][C:34](=[O:48])[CH2:35]/[C:36](=[CH:8]\[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:13]([CH3:23])[CH:12]=1)/[C:37]([O-:39])=[O:38])([CH3:32])([CH3:30])[CH3:31]

Participants

10

Reactant 6

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 111510303-(Diethoxyphosphoryl)succinic acid 1-tert-butyl esterHCID 23382482HCID 23382482, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 69911076HCID 69911076, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of potassium tert-butoxide (7.25 g, 64.6 mmol) in THF (24 ml) was added over 1 hour to a stirred solution of sodium 1-hydroxy-3-(2-methyl-1,1′-biphenyl-4-yl)-1-propanesulfonate (5.0 g, 15.2 mmol) and 3-(diethoxyphosphoryl)succinic acid 1-tert-butyl ester (5.5 g, 17.7 mmol) in THF (6 ml) and tert-butanol (30 ml), between −5 and 0° C., under nitrogen. The mixture was stirred between −5 and 0° C. for 4 hours and then a solution of citric acid (13.2 g) in demineralised water (132 ml) was added in one portion. The pH was adjusted to pH4-5 by the addition of aqueous sodium hydroxide solution (40%) and the organic phase was separated. The organic phase was concentrated in vacuo and then recombined with the aqueous phase. Ethyl acetate (55 ml) was added and the organic phase was separated and then washed with a solution of sodium bicarbonate (3.5 g) in demineralised water (50 ml). The organic phase was separated and washed with citric acid (5.0 g) in demineralised water (50 ml), demineralised water (50 ml) and then concentrated in vacuo to an orange oil. The oil was taken up in acetonitrile (30 ml) and a solution of sodium bicarbonate (0.65 g, 4.1 mmol) in demineralised water (5 ml) was added. The solution was azeotropically dried by distillation at a constant volume of acetonitrile and the mixture was granulated at 20-25° C. overnight. The mixture was filtered and the residue dried in vacuo at 45° C. to give the title compound as a white solid (2.6 g, 43% yield, 95% pure by NMR).

Workup

  1. customthe organic phase was separated
  2. concentrationThe organic phase was concentrated in vacuo
  3. additionEthyl acetate (55 ml) was added
  4. customthe organic phase was separated
  5. washwashed with a solution of sodium bicarbonate (3.5 g) in demineralised water (50 ml)
  6. customThe organic phase was separated
  7. washwashed with citric acid (5.0 g) in demineralised water (50 ml), demineralised water (50 ml)
  8. concentrationconcentrated in vacuo to an orange oil
  9. dry with materialThe solution was azeotropically dried by distillation at a constant volume of acetonitrile
  10. waitthe mixture was granulated at 20-25° C. overnight
  11. filtrationThe mixture was filtered
  12. customthe residue dried in vacuo at 45° C.

Sources & evidence

ORD record
ord-5df166f42e9e4dfda461acf0f6d3795c
Source dataset
uspto-grants-2004_06
Patent number
US06750363B2

Reaction notes

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