Pyridine → (S)-Cyclohex-1-enyl-hydroxy-phenyl-acetic acid

HRID 660082Notes

Reaction equation

HRID 660082 reaction equation
C([C@H]1[O:9][C:8](=[O:10])[C@@:7]([C:17]2(O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:6]1)(C)(C)C.S(Cl)(Cl)=O.N1C=CC=CC=1.[OH-].[K+]>C1COCC1>[C:17]1([C@:7]([OH:6])([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:8]([OH:10])=[O:9])[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 67538099(2R,5S)-2-tert-Butyl-5-(1-hydroxy-cyclohexyl)-5-phenyl-[1,3]dioxolan-4-one

Product 1

HCID 10585664(S)-Cyclohex-1-enyl-hydroxy-phenyl-acetic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(2R,5S)-2-tert-Butyl-5-(1-hydroxy-cyclohexyl)-5-phenyl-[1,3]dioxolan-4-one (176 g, 0.553 mol) in THF (1.56 litres) is cooled to 0° C. and treated dropwise with thionyl chloride (109 ml, 1.49 mol) followed by pyridine (191 ml, 2.35 mol) over 40 minutes. After stirring at 0° C. for 30 minutes, the reaction is quenched by dropwise addition of saturated ammonium chloride solution (2000 ml) ensuring the temperature does not exceed 25° C. Water (300 ml) is added and the organic portion is separated. The aqueous is extracted with EtOAc (1000 ml) and the combined organic layers are washed with brine and concentrated in vacuo. To the resulting crude material is added MeOH (333 ml) followed by water (586 ml). The mixture is stirred and treated with potassium hydroxide (221.2 g, 5.53 mol) maintaining the temperature below 50° C. The reaction mixture is heated to reflux for 3.5 hour and then allowed to cool to room temperature. The methanol is removed in vacuo and the aqueous is cooled to 0° C. The solution is acidified to pH1 with 5M HCl and then diluted with water (1 litre). The solution is extracted with EtOAc (2×1 litre) and the combined organic portions are dried (Na2SO4) and concentrated in vacuo to afford the titled product.

Workup

  1. customthe reaction is quenched by dropwise addition of saturated ammonium chloride solution (2000 ml)
  2. customdoes not exceed 25° C
  3. additionWater (300 ml) is added
  4. customthe organic portion is separated
  5. extractionThe aqueous is extracted with EtOAc (1000 ml)
  6. washthe combined organic layers are washed with brine
  7. concentrationconcentrated in vacuo
  8. additionTo the resulting crude material is added MeOH (333 ml)
  9. stirringThe mixture is stirred
  10. temperaturemaintaining the temperature below 50° C
  11. temperatureThe reaction mixture is heated
  12. temperatureto reflux for 3.5 hour
  13. temperatureto cool to room temperature
  14. customThe methanol is removed in vacuo
  15. temperaturethe aqueous is cooled to 0° C
  16. additiondiluted with water (1 litre)
  17. extractionThe solution is extracted with EtOAc (2×1 litre)
  18. dry with materialthe combined organic portions are dried (Na2SO4)
  19. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c289eca989964bafb3ed12eeab49dcad
Source dataset
uspto-grants-2011_12
Patent number
US08084463B2

Reaction notes

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