HCID 72281714, 화합물 → HCID 67000180, 화합물

HRID 559487

반응식

HRID 559487 반응식
[CH2:1]([O:3][C:4](=[O:20])[C:5]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([CH:17]2[CH2:19][CH2:18]2)(=[O:16])=[O:15])=[CH:10][CH:9]=1)=[N+]=[N-])[CH3:2]>ClCCl.C(C1CCCCC1)=C>[CH2:1]([O:3][C:4]([C@:5]1([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]3[CH2:19][CH2:18]3)(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH2:4][C@H:5]1[CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:20])[CH3:2]

참가 물질

4

반응물 1

HCID 72281714HCID 72281714, 화합물

생성물 1

HCID 67000180HCID 67000180, 화합물수율 201.2%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 12757Vinylcyclohexane용매2회

반응 조건

온도
40 °C

실험 절차

To a solution of vinylcyclohexane (300 mL, 2.72 mol) in 150 mL of anhydrous dichloromethane maintained at 25-30° C. under an inert atmosphere is added a solution of tetrakis[N-phthaloyl-(R)-tert-leucinato]dirhodium bis(ethylacetate) adduct (120 mg, 84 μmol) in vinylcyclohexane (40 mL) dropwise, while portions of (4-cyclopropanesulfonyl-phenyl)-diazo-acetic acid ethyl ester (169.40 g, 575.5 mmol) are added. The addition rates are adjusted to maintain an internal temperature of 40° C. The addition is complete after approximately 1.5 hours, and the reaction mixture is stirred for an additional 2 hours at 30° C. Volatiles are then removed under vacuum to afford crude (1R,2S)-2-cyclohexyl-1-(4-cyclopropanesulfonyl-phenyl)-cyclopropanecarboxylic acid ethyl ester as a viscous brown oil (218 g, 579 mmol) which is dissolved in 1.1 L of methanol to afford a yellow-brown solution, to which a 5 N aqueous sodium hydroxide solution (500 mL, 2.5 mmol) is added slowly. The resulting slurry is then stirred at 50° C. for 1 hour, during which time a solution forms. Methanol is removed under vacuum, and 1 L of ethylacetate is added. The resulting mixture is acidified by the addition of approximately 550 mL of 5% aqueous hydrochloric acid, and the two layers are separated. The aqueous layer is then extracted with two 500 mL portions of ethyl acetate. The organic phases are combined, washed with 500 mL of saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated to afford a moist pale yellow solid. This material is then dissolved in 1 L of methanol. Water (1 L) is then added to the stirred solution over the course of 1.5 hours. The resulting slurry is stirred at room temperature for 30 minutes, and then filtered. The filter pad is washed with 1:1 methanol/water, and dried to afford the title compound as pale yellow crystals (166 g). MS exact mass calculated 349.14735; found 349.14679 (Agilent 1100 LC-TOF using electrospray ionization); [α]D20=−31°.

후처리

  1. additionThe addition rates
  2. additionThe addition
  3. customVolatiles are then removed under vacuum

출처 및 근거

ORD 기록
ord-d84cc1e87a9843b7b9162833240e1061
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063079B2

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