Trifluoroacetic acid → HCID 67278023, Verbindung

HRID 1621230Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1621230
CC(O[C:6]([NH:8][C@@H:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[N:27]=[C:28]3[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][N:29]3[CH:35]=2)=[CH:22][CH:21]=1)[CH2:10][CH2:11][C:12]([O:14]C(C)(C)C)=[O:13])=[O:7])(C)C.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C(NC(C)C)(C)C.[Cl:57][C:58]1[CH:59]=[C:60]([CH:75]=[CH:76][C:77]=1[O:78][CH:79]([CH3:81])[CH3:80])C(OC1C(F)=C(F)C(F)=C(F)C=1F)=O>C(Cl)Cl>[Cl:57][C:58]1[CH:59]=[C:60]([C:6]([NH:8][C@@H:9]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]3[N:27]=[C:28]4[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][N:29]4[CH:35]=3)=[CH:24][CH:25]=2)[CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[O:7])[CH:75]=[CH:76][C:77]=1[O:78][CH:79]([CH3:81])[CH3:80]

Komponenten

7

Edukt 5

HCID 6422Trifluoroacetic acidHCID 7912DiisopropylamineHCID 12052TriethylsilaneHCID 57594128HCID 57594128, VerbindungHCID 672783711,1-dimethylethyl (4R)-4-(([(1,1-dimethylethyl)oxy]carbonyl}amino)-5-[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]pentanoate

Produkt 1

HCID 67278023HCID 67278023, VerbindungAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 1,1-dimethylethyl (4R)-4-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]pentanoate (1.35 g, 2.82 mmol) in CH2Cl2 (14 mL) was added trifluoroacetic acid (10 mL) followed by triethylsilane (2.5 equiv, 7.04 mmol). The reaction was stirred for 45 minutes at room temperature and then concentrated in vacuo. DMF (35 mL) was added to the residue followed by diisopropylamine (14.7 mL, 84.51 mmol) under nitrogen. The reaction was stirred for 5 minutes and pentafluorophenyl 3-chloro-4-[(1-methylethyl)oxy]benzoate (1.1 equiv, 3.10 mmol) was added. The reaction was stirred for 45 minutes and then concentrated in vacuo. Ethyl acetate (50 mL) was added to the residue and it was washed with H2O (30 mL). The aqueous layer was extracted with EtOAc (20 mL) and the combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification by silica gel chromatography (Analogix IF280, 25-100% EtOAc/hexanes) provided the title compound as a white foamy solid (61%). ESMS [M+H]+=520.2.

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. additionDMF (35 mL) was added to the residue
  3. stirringThe reaction was stirred for 5 minutes
  4. stirringThe reaction was stirred for 45 minutes
  5. concentrationconcentrated in vacuo
  6. additionEthyl acetate (50 mL) was added to the residue and it
  7. washwas washed with H2O (30 mL)
  8. extractionThe aqueous layer was extracted with EtOAc (20 mL)
  9. dry with materialthe combined organic layers were dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customPurification by silica gel chromatography (Analogix IF280, 25-100% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c9024c4e325f4446aa5b786fc4afc1d9
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772507B2

Notizen zur Reaktion

Wird geladen…