Water → Ethyl (1R,2S)-1-[[(1,1-dimethylethoxy)carbonyl]amino]-2-ethenylcyclopropanecarboxylate

HRID 544818

Reaction equation

HRID 544818 reaction equation
B([O-])([O-])[O-].[Na+].[Na+].[Na+].O.[OH-].[Na+].[CH2:11]([O:13][C:14]([C@:16]1([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][C@@H:17]1[CH:19]=[CH2:20])=[O:15])[CH3:12]>CS(C)=O>[CH2:11]([O:13][C:14]([C@@:16]1([NH:21][C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:18][C@H:17]1[CH:19]=[CH2:20])=[O:15])[CH3:12]

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium Hydroxide4×HCID 159383boric acid, sodium saltHCID 16067766Ethyl (1S,2R)-1-{[(tert-butoxy)carbonyl]amino}-2-ethenylcyclopropane-1-carboxylate

Product 1

HCID 10658673Ethyl (1R,2S)-1-[[(1,1-dimethylethoxy)carbonyl]amino]-2-ethenylcyclopropanecarboxylate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
48 °C

Procedure

A solution of 5 L of 0.2M sodium borate buffer (pH 9) at 45° C. in a 20 L jacked reactor stirred at 400 rpm was treated with 3 L of DI water and 4 L of Savinase 16 L, type EX (Novozymes North America Inc.). When the temperature of the mixture closed to 45° C., the pH was adjusted to 8.5 with 10N NaOH. A solution of (1R,2S)/(1S,2R)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester (200 grams) in 2 L DMSO was added to the reactor over a period of 40 minutes via addition funnel. The reaction temperature was then adjusted to 48° C. After 2 hours, the pH was adjusted to pH 9.0 with 10N NaOH. At 18 hours, enantio-excess of the ester reached 72% and the pH was adjusted to 9.0 with 10N NaOH. At 24 hours the temperature was lowered to 35° C. At 42 hours the temperature was raised to 48° C. and the pH was adjusted to 9.0 with 10N NaOH. Heating was stopped at 48 hours and the reaction was slowly cooled down to room temperature (about 25° C.) and stirred overnight. At 66 hours, the pH of the reaction mixture was 8.6. The mixture was extracted with MTBE (2×4 L). The combined MTBE extracts were washed with 5% NaHCO3 (6×300 mL) and water (3×300 mL) and concentrated to give enantiomerically pure (1R,2S)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester as light yellow crystals (101A g; purity: 95.9% (210 nm, containing no acid; 98.6% ee).

Workup

  1. customat 45° C.
  2. customWhen the temperature of the mixture closed to 45° C.
  3. customwas then adjusted to 48° C
  4. waitAt 18 hours
  5. waitAt 24 hours the temperature was lowered to 35° C
  6. temperatureHeating
  7. waitwas stopped at 48 hours
  8. temperaturethe reaction was slowly cooled down to room temperature (about 25° C.)
  9. stirringstirred overnight
  10. waitAt 66 hours
  11. extractionThe mixture was extracted with MTBE (2×4 L)
  12. washThe combined MTBE extracts were washed with 5% NaHCO3 (6×300 mL) and water (3×300 mL)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-641ed36f1ef745f48766df779a4afb37
Source dataset
uspto-grants-2011_05
Patent number
US07935670B2

Linked notes

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