Sodium Hydroxide → (2S,3R)-2,3-epoxy-3-cyclohexylpropionic acid

HRID 1376251Notes

Reaction equation

HRID 1376251 reaction equation
[O:1]1[C@H:12]([CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C@H:2]1[C:3]([O:5]C1C=CC=CC=1)=[O:4].[OH-].[Na+].O.O.P([O-])(O)(O)=O.[Na+]>CO>[O:1]1[C@H:12]([CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]2)[C@H:2]1[C:3]([OH:5])=[O:4]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 12115535HCID 12115535, compoundHCID 23673460Sodium Phosphate, Monobasic, Dihydrate

Product 1

HCID 11788529(2S,3R)-2,3-epoxy-3-cyclohexylpropionic acidYield 48.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

Into a 2,000 ml three-necked flask equipped with a dropping funnel and a stirrer, the phenyl (2S,3R)-2,3-epoxy-3-cyclohexylpropionate (54.0 g, 219 mmol) obtained in Example 2 and methanol (437 ml) were charged and cooled to 0° C. Then, a 4% sodium hydroxide aqueous solution (250 g, 250 mmol) was added thereto over a period of 1 hour, and the reaction was carried out for further 2 hours at the same temperature. After completion of the reaction, sodium dihydrogenphosphate dihydrate (3.42 g) was added, and then, the solvent was distilled off. Then, water (250 ml) was added, followed by extraction with dichloromethane (50 ml×4 times). Then, sodium dihydrogen phosphate dihydrate (116 g) was added, followed by extraction with ethyl acetate (50 ml×4 times). Then, a 10% hydrochloric acid aqueous solution (200 ml) was added, and the pH was adjusted to 3, followed by extraction with ethyl acetate (50 ml×3 times), drying and concentration, to obtain crude (2S,3R)-2,3-epoxy-3-cyclohexylpropionic acid (20.5 g). The obtained crude product was recrystallized from n-heptane/toluene=2/1 (vol/vol) to obtain the desired (2S,3R)-2,3-epoxy-3-cyclohexylpropionic acid (18.0 g, 106 mmol) (yield: 48%).

Workup

  1. customInto a 2,000 ml three-necked flask equipped with a dropping funnel and a stirrer
  2. waitthe reaction was carried out for further 2 hours at the same temperature
  3. additionwas added
  4. distillationthe solvent was distilled off
  5. additionThen, water (250 ml) was added
  6. extractionfollowed by extraction with dichloromethane (50 ml×4 times)
  7. additionThen, sodium dihydrogen phosphate dihydrate (116 g) was added
  8. extractionfollowed by extraction with ethyl acetate (50 ml×4 times)
  9. additionThen, a 10% hydrochloric acid aqueous solution (200 ml) was added
  10. extractionfollowed by extraction with ethyl acetate (50 ml×3 times)
  11. customdrying
  12. concentrationconcentration
  13. customto obtain crude (2S,3R)-2,3-epoxy-3-cyclohexylpropionic acid (20.5 g)
  14. customThe obtained crude product
  15. customwas recrystallized from n-heptane/toluene=2/1 (vol/vol)

Sources & evidence

ORD record
ord-bc3071a55e6f4fbca14413e6ecf4b901
Source dataset
uspto-grants-2007_01
Patent number
US07169944B2

Reaction notes

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