Citric Acid → 1-[2-(1,3-Dioxolan-2-yl)-1,3-thiazol-5-yl]-2,2,2-trifluoroethanol

HRID 1881885Notes

Reaction equation

HRID 1881885 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[S:7][CH:8]=[CH:9][N:10]=1.CCCCCC.C([Li])CCC.[F:22][C:23]([F:30])([F:29])[C:24](OCC)=[O:25].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[S:7][C:8]([CH:24]([OH:25])[C:23]([F:30])([F:29])[F:22])=[CH:9][N:10]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 9794Ethyl trifluoroacetateHCID 152051582-(1,3-Dioxolan-2-yl)-1,3-thiazoleHCID 178418244HCID 178418244, compound

Product 1

HCID 593313011-[2-(1,3-Dioxolan-2-yl)-1,3-thiazol-5-yl]-2,2,2-trifluoroethanolYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

To a solution of 2-(1,3-dioxolan-2-yl)-1,3-thiazole (2.00 g) in tetrahydrofuran (50 mL) was slowly added a 1.6M n-butyllithium hexane solution (8.7 mL) at −70° C. under a nitrogen atmosphere. The reaction mixture was stirred at −70° C. for 30 min, and ethyl trifluoroacetate (5.4 g) was added. The reaction mixture was warmed to room temperature, 10% aqueous citric acid solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was dissolved in methanol (30 mL), and sodium borohydride (0.27 g) was added by small portions at 0° C. The reaction mixture was stirred at 0° C. for 30 min, 10% aqueous citric acid solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was subjected to silica gel column chromatography, and the title compound (2.56 g, yield 79%) was obtained as a yellow oil from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). MS: 256 (MH+).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. dissolutionThe obtained residue was dissolved in methanol (30 mL)
  7. additionsodium borohydride (0.27 g) was added by small portions at 0° C
  8. stirringThe reaction mixture was stirred at 0° C. for 30 min
  9. addition10% aqueous citric acid solution was added
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with saturated brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-f72d3f43451046bc97d64b33f9325a6b
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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