Citric Acid → HCID 18630138, compound

HRID 725457Notes

Reaction equation

HRID 725457 reaction equation
[Li][CH:2](CC)C.C1CCCCC1.C[N:13]([CH2:15][CH2:16]N(C)C)C.Br[C:21]1[CH:29]=[CH:28][CH:27]=[C:26]([Si:30]([CH3:33])([CH3:32])[CH3:31])[C:22]=1[C:23]([OH:25])=O.CI.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[CH2:15]([NH:13][C:23](=[O:25])[C:22]1[C:26]([Si:30]([CH3:33])([CH3:32])[CH3:31])=[CH:27][CH:28]=[CH:29][C:21]=1[CH3:2])[CH3:16]

Participants

8

Reactant 6

HCID 311Citric AcidHCID 6328Methyl iodideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 8078CyclohexaneHCID 18630238HCID 18630238, compoundHCID 178418400CID 53628100

Product 1

HCID 18630138HCID 18630138, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1.3M s-BuLi in cyclohexane (25.4 mL, 0.033 mol) was added dropwise to THF (50 mL), TMEDA (3,83 g, 0.033 mol), and the compound of Example c (4.10 g, 0.015 mol), cooled to -78° under nitrogen with stirring. After stirring for 20 min, MeI (2.45 g, 0.01725 mol) was added all at once. The mixture was stirred for 1 h, and 25% citric acid (50 mL) was added. The mixture was extracted three times with CH2Cl2. The combined extracts were washed twice with water, dried (MgSO4), and concentrated. To the resulting mixture were added 30 mL thionyl chloride and 5 drops of DMF. After stirring at RT overnight, the mixture was concentrated to dryness; 50 mL toluene were added; and again the mixture was concentrated. This process was repeated 3 times. The crude product, a brown oil, was dissolved in 30 mL toluene and added to a 100 mL solution of 70% ethyl amine in water which had been cooled to 5° in an ice bath. After stirring overnight, the mixture was washed with 10% HCl and three times with water, dried (MgSO4), concentrated, and purified by HPLC eluting with 1:3 ethyl acetate/hexanes. Two fractions were obtained. When each was concentrated, Compound 48 crystallized as a white solid in a 20% yield. m.p. 115°-117° C. Compound 49 crystallized as a white solid in a 42% yield. m.p. 64°-66° C.

Workup

  1. stirringAfter stirring for 20 min
  2. stirringThe mixture was stirred for 1 h
  3. extractionThe mixture was extracted three times with CH2Cl2
  4. washThe combined extracts were washed twice with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. additionTo the resulting mixture were added 30 mL thionyl chloride and 5 drops of DMF
  8. stirringAfter stirring at RT overnight
  9. concentrationthe mixture was concentrated to dryness
  10. addition50 mL toluene were added
  11. concentrationand again the mixture was concentrated
  12. dissolutionThe crude product, a brown oil, was dissolved in 30 mL toluene
  13. additionadded to a 100 mL solution of 70% ethyl amine in water which
  14. temperaturehad been cooled to 5° in an ice bath
  15. stirringAfter stirring overnight
  16. washthe mixture was washed with 10% HCl and three times with water
  17. dry with materialdried (MgSO4)
  18. concentrationconcentrated
  19. custompurified by HPLC
  20. washeluting with 1:3 ethyl acetate/hexanes
  21. customTwo fractions were obtained
  22. concentrationWhen each was concentrated
  23. customCompound 48 crystallized as a white solid in a 20% yield
  24. customCompound 49 crystallized as a white solid in a 42% yield

Sources & evidence

ORD record
ord-6a6a82a197cf4906b1131dbdeb279832
Source dataset
uspto-grants-1998_01
Patent number
US05705513

Reaction notes

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