Cesium carbonate → 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

HRID 2075417

反応式

HRID 2075417 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:11]2[S:15][C:14]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[N:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].C(=O)([O-])[O-].[Cs+].[Cs+].[Si:30]([O:37][C@@H:38]([C:53]1[CH:58]=[CH:57][C:56]([C:59]([F:62])([F:61])[F:60])=[CH:55][CH:54]=1)[C@H:39]1[CH2:43]OS(=O)(=O)[N:40]1[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31].S1C=CN=N1>C1COCC1>[C:49]([O:48][C:46]([NH:40][C@@H:39]([C@@H:38]([O:37][Si:30]([C:33]([CH3:34])([CH3:36])[CH3:35])([CH3:31])[CH3:32])[C:53]1[CH:54]=[CH:55][C:56]([C:59]([F:62])([F:61])[F:60])=[CH:57][CH:58]=1)[CH2:43][N:16]([C:14]1[S:15][C:11]([C:4]2[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([F:1])[CH:3]=2)=[N:12][N:13]=1)[C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:47])([CH3:52])([CH3:51])[CH3:50]

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 675181,2,3-ThiadiazoleHCID 57991903tert-Butyl 5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-ylcarbamateHCID 58488199tert-Butyl (4R)-4-((S)-((tert-butyl(dimethyl)silyl)oxy)(4-(trifluoromethyl)phenyl)methyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

生成物 1

HCID 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収率 93.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
55 °C

実験手順

To a mixture of tert-butyl 5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-ylcarbamate (0.64 g, 1.89 mmol) in THF (6 mL) was added cesium carbonate (1.07 g, 3.28 mmol). The mixture was heated to 55° C. for 10 minutes and then tert-butyl (4R)-4-((S)-((tert-butyl(dimethyl)silyl)oxy)(4-(trifluoromethyl)phenyl)methyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (0.84 g, 1.64 mmol) in THF (4 mL) was added. The mixture was heated for 1 hour after the addition. HPLC-MS showed the product and thiadiazole starting material. The reaction was concentrated in vacuo and EtOAc (75 mL) was added. The mixture was cooled to 0° C. and 5% HCl (50 mL) was slowly added. The mixture was stirred for 1 hour. The organic phase was separated, and the aqueous phase was extracted twice with EtOAc. To the combined EtOAc solution was added saturated NaHCO3 and Na2CO3 until it was basic (pH=9). The organic layer was washed with brine, dried over Na2SO4, and then concentrated in vacuo. The residue was purified by chromatography on silica gel (50%-100% DCM-hexane) to provide the product as a yellow solid (1.18 g, 93%). LCMS (API-ES) m/z: 772 (M+H+).

後処理

  1. temperatureThe mixture was heated for 1 hour
  2. additionafter the addition
  3. concentrationThe reaction was concentrated in vacuo and EtOAc (75 mL)
  4. additionwas added
  5. temperatureThe mixture was cooled to 0° C.
  6. addition5% HCl (50 mL) was slowly added
  7. customThe organic phase was separated
  8. extractionthe aqueous phase was extracted twice with EtOAc
  9. additionTo the combined EtOAc solution was added saturated NaHCO3 and Na2CO3 until it
  10. washThe organic layer was washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by chromatography on silica gel (50%-100% DCM-hexane)

出典と根拠

ORDレコード
ord-76824737e9ce4ac6be6cf907f2504739
出典データセット
uspto-grants-2011_04
特許番号
US07919504B2

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