Diethyl Malonate → Diethyl (5-(5-((tert-butoxycarbonyl)((2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyl(dimethyl)silyl)oxy)-3-(4-(trifluoromethyl)phenyl)propyl)amino)-1,3,4-thiadiazol-2-yl)-2-nitrophenyl)propanedioate

HRID 2075418노트

반응식

HRID 2075418 반응식
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:14]([O:18][C:19]([NH:21][C@@H:22]([C@@H:47]([O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60])[C:48]1[CH:53]=[CH:52][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:50][CH:49]=1)[CH2:23][N:24]([C:32]1[S:33][C:34]([C:37]2[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[C:39](F)[CH:38]=2)=[N:35][N:36]=1)[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:20])([CH3:17])([CH3:16])[CH3:15]>O1CCOCC1>[C:27]([O:26][C:25]([N:24]([CH2:23][C@@H:22]([NH:21][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])[C@@H:47]([O:58][Si:59]([C:62]([CH3:63])([CH3:64])[CH3:65])([CH3:61])[CH3:60])[C:48]1[CH:53]=[CH:52][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:50][CH:49]=1)[C:32]1[S:33][C:34]([C:37]2[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[C:39]([CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH:38]=2)=[N:35][N:36]=1)=[O:31])([CH3:28])([CH3:29])[CH3:30]

참가 물질

5

반응물 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 57991858tert-Butyl ((2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyl(dimethyl)silyl)oxy)-3-(4-(trifluoromethyl)phenyl)propyl)(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl)carbamate

생성물 1

HCID 57991937Diethyl (5-(5-((tert-butoxycarbonyl)((2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyl(dimethyl)silyl)oxy)-3-(4-(trifluoromethyl)phenyl)propyl)amino)-1,3,4-thiadiazol-2-yl)-2-nitrophenyl)propanedioate수율 99.4%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매3회

실험 절차

To a solution of sodium hydride (60% dispersion in mineral oil, 0.15 g, 3.74 mmol) in dioxane (2 mL) was added a solution of diethyl malonate (0.57 mL, 3.74 mmol) in dioxane (3 mL). The mixture was stirred for 15 minutes and then a solution of tert-butyl ((2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyl(dimethyl)silyl)oxy)-3-(4-(trifluoromethyl)phenyl)propyl)(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl)carbamate (0.58 g, 0.75 mmol) in dioxane (3 mL) was added. The reaction mixture was stirred 16 hours, concentrated in vacuo, and the reaction was quenched with saturated NH4Cl. The mixture was extracted with EtOAc three times. The organic phase was dried over Na2SO4, concentrated in vacuo and purified by chromatography on silica gel (0-15% EtOAc-hexane) to provide the product as a yellow solid (0.68 g, 99%). LCMS (API-ES) m/z: 856 (M+H+-56).

후처리

  1. stirringThe reaction mixture was stirred 16 hours
  2. concentrationconcentrated in vacuo
  3. customthe reaction was quenched with saturated NH4Cl
  4. extractionThe mixture was extracted with EtOAc three times
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. custompurified by chromatography on silica gel (0-15% EtOAc-hexane)

출처 및 근거

ORD 기록
ord-1f68fabb9c62409b89dbd311f95fe1e7
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919504B2

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