Pivaloyl chloride → HCID 91192837, Verbindung

HRID 397993

Reaktionsgleichung

Reaktionsgleichung von HRID 397993
[CH2:1]([NH:9][C:10]1[N:18]=[C:17]([NH:19][CH2:20][CH2:21][C:22]2[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=2)[N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[C@H:28]1[C@@H:32]2[O:33]C(C)(C)[O:35][C@@H:31]2[C@@H:30]([C:38]([OH:40])=O)[O:29]1)[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.CC(C)(C)[C:52](Cl)=[O:53].O[NH:58][C:59](=[NH:62])[CH2:60][CH3:61].C(Cl)Cl.C1C[O:69][CH2:68]C1>FC(F)(F)C(O)=O.O>[CH:68]([O:33][C@@H:32]1[C@H:31]([O:35][CH:52]=[O:53])[C@@H:30]([C:38]2[O:40][N:62]=[C:59]([CH2:60][CH3:61])[N:58]=2)[O:29][C@H:28]1[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][C:17]([NH:19][CH2:20][CH2:21][C:22]1[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=1)=[N:18][C:10]=2[NH:9][CH2:1][CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:69]

Komponenten

7

Edukt 5

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 21919333Tetrahydrofurane dichloromethaneHCID 70021813HCID 70021813, VerbindungHCID 178458070HCID 178458070, Verbindung

Produkt 1

HCID 91192837HCID 91192837, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 22392675Trifluoroacetic acid waterLösungsmittel

Versuchsvorschrift

Intermediate 34 (0.083 mg, 0.15 mmol) was dissolved in DCM/THF (9:1, 3 ml) using sonication by ultrasound. N,N-diisopropylethylamine (0.057 ml, 3.32 mmol) and trimethylacetyl chloride (0.021 ml, 0.16 mmol) were added at 0° C. with stirring under nitrogen. The reaction was allowed to warm to room temperature over 2 h, cooled again to 0° C. and N-hydroxy-propionamidine (0.015 g, 0.18 mmol in 0.5 ml tetrahydrofuran) added with stirring. The reaction was allowed to warm to room temperature and stirred for 16 h. The solvents were evaporated in vacuo and the reaction mixture dissolved in toluene (10 ml). The reaction was heated to reflux (120° C.) for 8 h. The product was purified on a Varian Mega Bond Elut cartridge (5 g Si, 20 ml size) eluting with ethyl acetate/methanol (50:1-1:1) to afford crude product as a yellow oil (0.01 g). The product dissolved in trifluoroacetic acid/water (4 ml, 9:1) at 0° C. with stirring under nitrogen for 4 h. The solvents were evaporated in vacuo, azeotroped with toluene (2×50 ml) and purification using Autoprep. HPLC afforded title compound as yellow gum (0.004 g) LCMS SYSTEM C Rt=2.39 min m/z=561 MH+

Aufarbeitung

  1. customsonication by ultrasound
  2. temperaturecooled again to 0° C.
  3. stirringwith stirring
  4. temperatureto warm to room temperature
  5. stirringstirred for 16 h
  6. customThe solvents were evaporated in vacuo
  7. dissolutionthe reaction mixture dissolved in toluene (10 ml)
  8. temperatureThe reaction was heated
  9. temperatureto reflux (120° C.) for 8 h
  10. customThe product was purified on a Varian Mega Bond Elut cartridge (5 g Si, 20 ml size)
  11. washeluting with ethyl acetate/methanol (50:1-1:1)
  12. customto afford crude product as a yellow oil (0.01 g)
  13. stirringwith stirring under nitrogen for 4 h
  14. customThe solvents were evaporated in vacuo
  15. customazeotroped with toluene (2×50 ml) and purification

Quellen und Nachweise

ORD-Eintrag
ord-9897c69ee8f946ec83c949718f6abc9d
Quelldatensatz
uspto-grants-2003_08
Patentnummer
US06610665B1

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