Water → (2-(4-(Trifluoromethyl)phenyl)thiazole-4,5-diyl)dimethanol

HRID 270160Notes

Reaction equation

HRID 270160 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]([F:31])([F:30])[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:16][C:17]([C:25](OCC)=[O:26])=[C:18]([C:20](OCC)=[O:21])[N:19]=2)=[CH:11][CH:10]=1.S(=O)(=O)(O)O.O>C1COCC1.C(OCC)(=O)C.ClCCl>[OH:26][CH2:25][C:17]1[S:16][C:15]([C:12]2[CH:11]=[CH:10][C:9]([C:8]([F:31])([F:30])[F:7])=[CH:14][CH:13]=2)=[N:19][C:18]=1[CH2:20][OH:21]

Participants

8

Reactant 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 11975782Diethyl 2-(4-(trifluoromethyl)phenyl)thiazole-4,5-dicarboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 11974006(2-(4-(Trifluoromethyl)phenyl)thiazole-4,5-diyl)dimethanol

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of lithium aluminum hydride (0.14wt) in THF (3.4vols), add a solution of the diethyl 2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-4,5-dicarboxylate (1.0wt, 1.0eq), dissolved in THF (2vols) at a rate such that the temperature of the reaction mixture is maintained at below −10° C. The addition time is 1.5-3.0hr. After the addition is complete, stir the reaction mixture at ambient temperature for 18h. Quench the reaction by adding aqueous 16% sulfuric acid (2.4vols). Charge ethyl acetate (5vols) with stirring to the reaction mixture followed with water (5vols). Filter the resulting two phase mixture through celite (0.4wt). Separate the layers and wash the organic layer with water (4×4vols) and with brine (2×4vol). Reduce the total volume of the reaction mixture via vacuum distillation to leave the solid suspended in ethyl acetate (1-1.5vols). Dilute the slurry with dichloromethane (5vols) and stir the suspension for at least 6h. Filter the tan-colored solid. Wash the wet cake with dichloromethane (2vols) and dry the wet cake at 45° C. under mild vacuum to afford the title compound as an off-white solid.

Workup

  1. temperatureis maintained at below −10° C
  2. additionAfter the addition
  3. customQuench
  4. customthe reaction
  5. filtrationFilter the resulting two phase mixture through celite (0.4wt)
  6. customSeparate the layers
  7. washwash the organic layer with water (4×4vols)
  8. distillationReduce the total volume of the reaction mixture via vacuum distillation
  9. customto leave the solid
  10. stirringstir the suspension for at least 6h
  11. filtrationFilter the tan-colored solid
  12. washWash the wet cake with dichloromethane (2vols)
  13. customdry the wet cake at 45° C. under mild vacuum

Sources & evidence

ORD record
ord-a087acc270524497ac98b7705fc3001a
Source dataset
uspto-grants-2008_11
Patent number
US07449468B2

Reaction notes

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