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

HRID 544817

反応式

HRID 544817 の反応式
P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].[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]>O.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]

参加物

6

反応物 3

HCID 14798Sodium Hydroxide3 回HCID 24243Trisodium PhosphateHCID 16067766Ethyl (1S,2R)-1-{[(tert-butoxy)carbonyl]amino}-2-ethenylcyclopropane-1-carboxylate

生成物 1

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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒2 回

反応条件

温度
39 °C

実験手順

To an aqueous solution of sodium phosphate buffer (0.1M, 4.25 L, pH 8) housed in a 12 Liter jacked reactor, maintained at 39° C., and stirred at 300 rpm, was added 511 grams of Alcalase 2.4 L (about 425 mL) (Novozymes North America Inc.). When the temperature of the mixture reached 39° C., the pH was adjusted to 8.0 by the addition of 50% NaOH in water. A solution of (1R,2S)/(1S,2R)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester (85 g) in 850 mL of DMSO was then added over a period of 40 minutes. The reaction temperature was maintained at 40° C. for 24.5 hours during which time the pH of the mixture was adjusted to 8.0 at the 1.5 hour and 19.5 hour time points using 50% NaOH in water. After 24.5 hours, the enantio-excess of the ester was determined to be 97.2%, and the reaction was cooled to room temperature (26° C.) and stirred overnight (16 hours) at which time the enantio-excess of the ester was determined to be 100%. The pH of the reaction mixture was then adjusted to 8.5 with 50% NaOH and the resulting mixture was extracted with MTBE (2×2 L). The combined MTBE extract was washed with 5% NaHCO3 (3×100 mL), water (3×100 mL), and then concentrated in vacuo to give the enantiomerically pure (1R,2S)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester as light yellow solid (42.55 g; purity: 97% (210 nm, containing no acid; 100% enantiomeric excess (“ee”).

後処理

  1. additionwas added 511 grams of Alcalase 2.4 L (about 425 mL) (Novozymes North America Inc.)
  2. customreached 39° C.
  3. temperatureThe reaction temperature was maintained at 40° C. for 24.5 hours during which time the pH of the mixture
  4. customwas adjusted to 8.0 at the 1.5 hour and 19.5 hour time points
  5. temperaturethe reaction was cooled to room temperature (26° C.)
  6. extractionthe resulting mixture was extracted with MTBE (2×2 L)
  7. extractionThe combined MTBE extract
  8. washwas washed with 5% NaHCO3 (3×100 mL), water (3×100 mL)
  9. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-08434296efb14e3e81912c021ab9d8d9
出典データセット
uspto-grants-2011_05
特許番号
US07935670B2

関連ノート

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