2,6-Lutidine → tert-butyl (2R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

HRID 629698

Reaktionsgleichung

Reaktionsgleichung von HRID 629698
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C@H:10]1[O:15][CH2:14][C@@H:13]([CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[N:12]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:11]1.[CH3:32][O:33][C:34]([NH:36][C@H:37]([C:51](O)=[O:52])[CH:38]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1C(C)=CC=CC=1C>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Si:18]([O:17][CH2:16][C@H:13]1[N:12]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:11][C@@H:10]([CH2:9][CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[NH:1][C:51](=[O:52])[C@H:37]([CH:38]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[NH:36][C:34]([O:33][CH3:32])=[O:35])[O:15][CH2:14]1)([C:21]([CH3:22])([CH3:23])[CH3:24])([CH3:19])[CH3:20]

Komponenten

8

Edukt 4

HCID 79372,6-LutidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10017620(S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acidHCID 86726305tert-butyl (2R,5S)-2-[2-(2-aminophenyl)ethyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate

Produkt 1

HCID 86726306tert-butyl (2R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

To tert-butyl (2R,5S)-2-[2-(2-aminophenyl)ethyl]-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)morpholine-4-carboxylate (1 eq.) in DMF (0.15 M) at rt was added N-(methoxycarbonyl)-β-phenyl-L-phenylalanine (1.1 eq.), HATU (1.4 eq.) and 2,6-lutidine (3 eq.). The reaction mixture was stirred at rt for 16 h and diluted with EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by automated SiO2 flash chromatography system using solvent gradient of 10% to 100% EtOAc/Hex to afford the desired compound.

Aufarbeitung

  1. extractionThe aqueous layer was extracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by automated SiO2 flash chromatography system

Quellen und Nachweise

ORD-Eintrag
ord-0da9f206408f474ab45774fe38a14ff5
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315475B2

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