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

Reaktionsgleichung

Reaktionsgleichung von HRID 2075417
[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]

Komponenten

6

Edukt 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

Produkt 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)carbamateAusbeute 93,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

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+).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-76824737e9ce4ac6be6cf907f2504739
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919504B2

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