Diisopropylethylamine → HCID 67500871, Verbindung

HRID 1631316Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1631316
O[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]#[N:12])=[C:4]2[N:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[F:40][C:41]1[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=1[C@H:48]1[CH2:52][CH2:51][CH2:50][NH:49]1.C(N(C(C)C)CC)(C)C>O.CN(C=O)C>[F:40][C:41]1[CH:46]=[CH:45][C:44]([F:47])=[CH:43][C:42]=1[C@H:48]1[CH2:52][CH2:51][CH2:50][N:49]1[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]#[N:12])=[C:4]2[N:3]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 71762902-(2,5-Difluorophenyl)pyrrolidine, (R)-HCID 178510451HCID 178510451, Verbindung

Produkt 1

HCID 67500871HCID 67500871, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A flask was charged with the product from Step A (2.80 g, 17.5 mmol), benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (9.28 g, 21.0 mmol) and dry DMF (35 mL). The suspension was stirred at ambient temperature for 2 minutes and (R)-2-(2,5-difluorophenyl)pyrrolidine (Preparation A, 3.84 g, 21.0 mmol) and diisopropylethylamine (6.78 g, 62.5 mmol) were sequentially added (mild exotherm). The mixture was stirred at ambient temperature for 3 hours and poured into H2O (175 mL). The mixture was extracted with 50% EtOAc-hexanes and the combined organic fractions were washed sequentially with 1M HCl, H2O, 1M Na2CO3 and saturated NaCl. The solution was dried over MgSO4/activated carbon and filtered through a short SiO2 plug (350 mL course frit funnel, ¼ full of SiO2, capped with a layer of MgSO4) using 50% EtOAc-hexanes for elution. The solution was concentrated to give the title compound as a brittle white foam that was crushed to a flowing white solid and dried in vacuum (5.50 g, 97%). MS (apci) m/z=326.2 (M+H).

Aufarbeitung

  1. stirringThe mixture was stirred at ambient temperature for 3 hours
  2. extractionThe mixture was extracted with 50% EtOAc-hexanes
  3. washthe combined organic fractions were washed sequentially with 1M HCl, H2O, 1M Na2CO3 and saturated NaCl
  4. dry with materialThe solution was dried over MgSO4/activated carbon
  5. filtrationfiltered through a short SiO2 plug (350 mL course frit funnel
  6. customfull of SiO2, capped with a layer of MgSO4)
  7. washfor elution
  8. concentrationThe solution was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-8a69ea9cbd984838a8ca11f84bd75978
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791123B2

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