Potassium Sodium Tartrate → 4-Thiazoleethanol, 2-(4-chlorophenyl)-

HRID 601496Notes

Reaction equation

HRID 601496 reaction equation
C([O:3][C:4](=O)[CH2:5][C:6]1[N:7]=[C:8]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[S:9][CH:10]=1)C.CC(C[AlH]CC(C)C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1.C1(C)C=CC=CC=1>[Cl:17][C:14]1[CH:13]=[CH:12][C:11]([C:8]2[S:9][CH:10]=[C:6]([CH2:5][CH2:4][OH:3])[N:7]=2)=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 9357Potassium Sodium TartrateHCID 14487Diisobutylaluminum hydride2×HCID 1522972-(4-Chlorophenyl)-4-thiazoleacetic acid ethyl ester

Product 1

HCID 6105314-Thiazoleethanol, 2-(4-chlorophenyl)-Yield 110%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2.5 °C

Procedure

Dissolve [2-(4-chloro-phenyl)-thiazol-4-yl]-acetic acid ethyl ester (107.4 g, 381.2 mmol) in THF (800 mL) and cool to 0-5° C. Add DIBAL (1.0 M in THF, 800 mL, 800 mmol) slowly over approximately 3.5 h (somewhat exothermic) keeping the temp. <5° C. Allow the reaction to warm to room temperature with mechanical stirring overnight. Cool the reaction to 0-5° C. and slowly add more DIBAL (150 mL) over approximately 15 min keeping the temperature <5° C. Stir the reaction solution at room temperature for 2.5 b. Cool to 0-5° C. and slowly add over 5 h aqueous saturated Rochelle's salt (2900 mL, very exothermic at first, minor gas evolution) keeping the temperature <10° C. The mixture solidifies after approximately 150 mL has been added. It becomes more fluid and then solidifies again as the addition continues. Extract the mixture with EtOAc (2×3300 mL). Combine the organic layers and concentrate in vacuo to give an oil weighing 112.9 g. Take the oil up in toluene (600 mL), concentrate in vacuo and repeat. Dry the residue on a vacuum pump for 6 h to give a residue weighing 107.4 g (110% yield). MS (ES+) 240.1 (M)+. 1H NMR (400 MHz, CDCl3): δ 7.84 (dt, J=8.4, 2.2 Hz, 2H), 7.39 (dt, J=8.4, 2.2 Hz, 2H), 6.98 (s, 1H), 3.98 (m, 2H), 3.44 (bs, 1H), 3.02 (t, J=5.5 Hz, 2H).

Workup

  1. custom<5° C
  2. customthe reaction
  3. temperatureto warm to room temperature
  4. temperatureCool
  5. customthe reaction to 0-5° C.
  6. customthe temperature <5° C
  7. stirringStir the reaction solution at room temperature for 2.5 b
  8. temperatureCool to 0-5° C.
  9. customthe temperature <10° C
  10. additionhas been added
  11. additionsolidifies again as the addition
  12. extractionExtract the mixture with EtOAc (2×3300 mL)
  13. concentrationCombine the organic layers and concentrate in vacuo
  14. customto give an oil
  15. concentrationconcentrate in vacuo and repeat
  16. customDry the residue on a vacuum pump for 6 h
  17. customto give a residue

Sources & evidence

ORD record
ord-1255c30e7cdc4f40ad0b4509c81ea2d8
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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