Toluene → HCID 10993936, compound

HRID 1584352Notes

Reaction equation

HRID 1584352 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:30])=[C:9]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16](CCCC(OC(C)C)=O)=[CH:15][C:14]=2[O:28][CH3:29])[N:10]=1.CN(C)C=O.[C:36]([O:44][CH:45]([CH3:47])[CH3:46])(=[O:43])[C:37]([O:39]C(C)C)=O.[H-].[Na+].[C:50]1(C)[CH:55]=CC=C[CH:51]=1>C(OCC)(=O)C>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:30])=[C:9]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([CH2:51][CH2:50][CH2:55][CH:37]([OH:39])[C:36]([O:44][CH:45]([CH3:46])[CH3:47])=[O:43])=[CH:15][C:14]=2[O:28][CH3:29])[N:10]=1

Participants

7

Reactant 5

HCID 1140Toluene2×HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 69209Diisopropyl oxalateHCID 11101724HCID 11101724, compound

Product 1

HCID 10993936HCID 10993936, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of isopropyl 4-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]-3-methoxyphenyl]butanoate (100 g) in toluene (30 ml)-N,N-dimethylformamide (DMF) (30 ml) was added dropwise, at 100° C., to a mixture of diisopropyl oxalate (84.3 g), sodium hydride (60% oil, 11.6 g) and toluene (300 ml)-N,N-dimethylformamide (DMF) (30 ml). The mixture was stirred for one hour at the same temperature, which was distributed into ice-water-2N HCl and ethyl acetate. The ethyl acetate layer separated was washed with water, dried (MgSO4) and then concentrated. The concentrate was dissolved in dimethyl sulfoxide (DMSO) (400 ml)-water (40 ml), to which was added sodium chloride (14.1 g). The mixture was stirred for 10 hours at 120° C. The reaction mixture was poured into water, which was subjected to extraction with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4) and then concentrated. The concentrate was dissolved in tetrahydrofuran (100 ml)-isopropanol (200 ml), to which was added portionwise sodium borohydride (NaBH4) (1.83 g) under ice-cooling. The reaction mixture was stirred for 90 minutes at 0° C., which was poured into ice-water and acidified with 2N HCl, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4) and then concentrated. The residue was subjected to column chromatography on silica gel. From the fraction eluted with ethyl acetate-hexane (1:2), was obtained isopropyl (±)-5-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]-3-methoxyphenyl]-2-hydroxypentanoate (35.1 g, 33%), which was recrystallized from ethyl acetate-hexane to give colorless prisms, m.p.75-76° C.

Workup

  1. customThe ethyl acetate layer separated
  2. washwas washed with water
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. dissolutionThe concentrate was dissolved in dimethyl sulfoxide (DMSO) (400 ml)-water (40 ml)
  6. additionto which was added sodium chloride (14.1 g)
  7. stirringThe mixture was stirred for 10 hours at 120° C
  8. additionThe reaction mixture was poured into water, which
  9. extractionwas subjected to extraction with ethyl acetate
  10. washThe ethyl acetate layer was washed with water
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. dissolutionThe concentrate was dissolved in tetrahydrofuran (100 ml)-isopropanol (200 ml)
  14. additionto which was added portionwise sodium borohydride (NaBH4) (1.83 g) under ice-
  15. temperaturecooling
  16. stirringThe reaction mixture was stirred for 90 minutes at 0° C.
  17. additionwhich was poured into ice-water
  18. extractionfollowed by extraction with ethyl acetate
  19. washThe ethyl acetate layer was washed with water
  20. dry with materialdried (MgSO4)
  21. concentrationconcentrated
  22. washFrom the fraction eluted with ethyl acetate-hexane (1:2)

Sources & evidence

ORD record
ord-4b42c78862a142899ee90d908df7a8c1
Source dataset
uspto-grants-1999_08
Patent number
US05932601

Reaction notes

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