Ethyl Acetate → rac-ethyl (1R,2S)-1-amino-2-ethenylcyclopropane-1-carboxylate

HRID 2174446Notes

Reaction equation

HRID 2174446 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@:13]1([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:15][C@H:14]1[CH:16]=[CH2:17].C(OCC)(=O)C.C(=O)(O)[O-].[K+]>O>[NH2:12][C@:13]1([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:15][C@H:14]1[CH:16]=[CH2:17]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 516893Potassium Bicarbonate2×HCID 46737761(1R,2S)-ethyl 1-amino-2-vinylcyclopropanecarboxylate 4-methylbenzenesulfonate

Product 1

HCID 10820795rac-ethyl (1R,2S)-1-amino-2-ethenylcyclopropane-1-carboxylateYield 95.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
6 °C

Procedure

498.4 g (content: 484.49 g, 1.48 mol) out of the (1R,2S)-1-amino-1-ethoxycarbonyl-2-vinylcyclopropane p-toluenesulfonate obtained in Example 29 and 2.1915 kg of ethyl acetate were added into a 10-L separable flask, and the obtained mixture was then cooled to 6° C. To this mixture, a potassium bicarbonate aqueous solution consisting of 220.04 g (2.2259 mol) of potassium bicarbonate and 971.7 g of water was added dropwise over 20 minutes, so as to separate (1R,2S)-1-amino-1-ethoxycarbonyl-2-vinylcyclopropane. The mixture was stirred for 1 hour, while maintaining the temperature at 6° C., so that an ethyl acetate layer was separated. To a water layer, 48.54 g of sodium chloride and 876.8 g of ethyl acetate were added, and the obtained mixture was then stirred at 6° C. for 1 hour 20 minutes. Thereafter, an ethyl acetate layer was separated. After this operation, 438.3 g of ethyl acetate was added to the obtained water layer, the obtained mixture was then stirred at 26° C. for 1 hour, and an ethyl acetate layer was then separated. This operation was repeatedly carried out three times. All of the ethyl acetate layers were gathered in a 10-L separable flask, and the gathered layer was then cooled to 6° C. Then, 121.47 g of sodium sulfate was added thereto, and the obtained mixture was then stirred for 30 minutes. The sodium sulfate was then removed by filtration. The sodium sulfate was washed with 438.3 g of ethyl acetate, and the washing solution was then mixed with the filtrate, so as to obtain an ethyl acetate solution of (1R,2S)-1-amino-1-ethoxycarbonyl-2-vinylcyclopropane. As a result of analysis by HPLC, the content of the (1R,2S)-1-amino-1-ethoxycarbonyl-2-vinylcyclopropane was found to be 212.86 g (yield: 95.1%).

Workup

  1. additionwas added dropwise over 20 minutes
  2. customso as to separate (1R,2S)-1-amino-1-ethoxycarbonyl-2-vinylcyclopropane
  3. temperaturewhile maintaining the temperature at 6° C.
  4. customso that an ethyl acetate layer was separated
  5. additionTo a water layer, 48.54 g of sodium chloride and 876.8 g of ethyl acetate were added
  6. stirringthe obtained mixture was then stirred at 6° C. for 1 hour 20 minutes
  7. customThereafter, an ethyl acetate layer was separated
  8. additionAfter this operation, 438.3 g of ethyl acetate was added to the obtained water layer
  9. stirringthe obtained mixture was then stirred at 26° C. for 1 hour
  10. customan ethyl acetate layer was then separated
  11. customAll of the ethyl acetate layers were gathered in a 10-L separable flask
  12. temperaturethe gathered layer was then cooled to 6° C
  13. additionThen, 121.47 g of sodium sulfate was added
  14. stirringthe obtained mixture was then stirred for 30 minutes
  15. customThe sodium sulfate was then removed by filtration
  16. washThe sodium sulfate was washed with 438.3 g of ethyl acetate
  17. additionthe washing solution was then mixed with the filtrate

Sources & evidence

ORD record
ord-b0eb51defc5c41caae27705f06276d64
Source dataset
uspto-grants-2015_06
Patent number
US09061991B2

Reaction notes

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