1,2-Dichloroethane → 3-Hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionylamino}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 460405노트

반응식

HRID 460405 반응식
[N:1]1([C:7]([NH:9][CH:10]([CH2:14][S:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:17])=[O:16])[C:11](O)=[O:12])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:25]([O:29][C:30]([N:32]1[CH2:36][CH:35]([OH:37])[CH:34]([NH2:38])[CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>ClCCl>[C:25]([O:29][C:30]([N:32]1[CH2:33][CH:34]([NH:38][C:11](=[O:12])[CH:10]([NH:9][C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)=[O:8])[CH2:14][S:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:17])=[O:16])[CH:35]([OH:37])[CH2:36]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 11229445tert-Butyl 3-amino-4-hydroxypyrrolidine-1-carboxylateHCID 112797342-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid

생성물 1

HCID 694401533-Hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionylamino}-pyrrolidine-1-carboxylic acid tert-butyl ester수율 69.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

2-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid (1 g, 2.8 mmol), 3-amino-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (700 mg, 3.46 mmol) prepared as in Reference 1, EDC (1.5 g, 7.8 mmol), and HOBt (1.5 g, 9.6 mmol) were combined. Dichloromethane (10 mL) was added and then 4-methylmorpholine (1.5 mL). The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (200 mL) the solution was washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL), dried with MgSO4 and evaporated under vacuum. 3-Hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionylamino}-pyrrolidine-1-carboxylic acid tert-butyl ester (1.05 g, 1.94 mmol) was obtained as yellowish foam and was dissolved in dichloromethane (6 mL). Trifluoroacetic acid (6 mL) was added and the mixture was stirred at ambient temperature for 1 hour. Evaporation under vacuum gave crude morpholine-4-carboxylic acid [1-(4-hydroxy-pyrrolidin-3-ylcarbamoyl)-2-phenylmethanesulfonyl-ethyl]-amide as TFA salt, which was used without further purification.

후처리

  1. washAfter dilution with ethyl acetate (200 mL) the solution was washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL)
  2. dry with materialdried with MgSO4
  3. customevaporated under vacuum

출처 및 근거

ORD 기록
ord-ca8a734dc5884a048cb832753fd83f02
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07196099B2

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