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 2075418ノート

反応式

HRID 2075418 の反応式
[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]

参加物

5

反応物 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

生成物 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)propanedioate収率 99.4%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒3 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-1f68fabb9c62409b89dbd311f95fe1e7
出典データセット
uspto-grants-2011_04
特許番号
US07919504B2

反応ノート

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