Citric Acid → (2S,3S)-(-)-3-tert-Butoxycarbonylamino-1,2-epoxy-4-phenylbutane

HRID 1841657Notes

Reaction equation

HRID 1841657 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C@H:10]([OH:13])[CH2:11]Cl)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C@@H:10]1[O:13][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 71466451,1-Dimethylethyl N-((1S,2S)-3-chloro-2-hydroxy-1-(phenylmethyl)propyl)carbamate

Product 1

HCID 9903372(2S,3S)-(-)-3-tert-Butoxycarbonylamino-1,2-epoxy-4-phenylbutaneYield 95%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Conditions

Temperature
33 °C

Procedure

(2S,3S)-3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane (5.29 g) and potassium carbonate (4.88 g) were added to an ethanol:water (97:3) mixed solution (106 ml). The mixture was stirred at 33° C. for 7 hours, and a 10% citric acid aqueous solution (67.8 g) was added thereto. After ethanol was distilled off under reduced pressure, toluene (93 ml) was added to conduct extraction. Further, the organic layer was washed with water (93 ml), and then concentrated. To the residue was added a heptane:toluene (4:1) mixture (112 ml). The heating was conducted at 50° C. over 1 hour, and the stirring was further conducted at 50° C. for 1 hour. Subsequently, cooling was conducted to −10° C. over 5 hours, and stirring was further conducted at −10° C. for 8 hours. Crystals were collected by filtration, washed with heptane, and then dried under reduced pressure to obtain desired (2S,3S)-3-tert-butoxycarbonylamino-1,2-epoxy-4-phenylbutane (4.39 g) in a yield of 95%.

Workup

  1. distillationAfter ethanol was distilled off under reduced pressure, toluene (93 ml)
  2. additionwas added
  3. extractionextraction
  4. washFurther, the organic layer was washed with water (93 ml)
  5. concentrationconcentrated
  6. additionTo the residue was added a heptane:toluene (4:1) mixture (112 ml)
  7. waitThe heating was conducted at 50° C. over 1 hour
  8. waitthe stirring was further conducted at 50° C. for 1 hour
  9. temperatureSubsequently, cooling
  10. waitwas conducted to −10° C. over 5 hours
  11. stirringstirring
  12. waitwas further conducted at −10° C. for 8 hours
  13. filtrationCrystals were collected by filtration
  14. washwashed with heptane
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-d759929aaadf4156bb66ec29ee1deedd
Source dataset
uspto-grants-2004_01
Patent number
US06683214B2

Reaction notes

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