Diisopropylethylamine → tert-Butyl (3R,4S)-3-{[[3-{[tert-butyl(dimethyl)silyl]oxy}-5-(3-methoxy-propyl)benzyl](cyclopropyl)amino]carbonyl}-4-{4-[2-(2,6-dichloro-4-methyl-phenoxy)ethoxy]phenyl}piperidine-1-carboxylate

HRID 658253Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 658253
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][O:23][C:24]3[C:29]([Cl:30])=[CH:28][C:27]([CH3:31])=[CH:26][C:25]=3[Cl:32])=[CH:16][CH:15]=2)[C@@H:10]([C:33]([OH:35])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Si:36]([O:43][C:44]1[CH:45]=[C:46]([CH:52]=[C:53]([CH2:55][CH2:56][CH2:57][O:58][CH3:59])[CH:54]=1)[CH2:47][NH:48][CH:49]1[CH2:51][CH2:50]1)([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CCOCC>[Si:36]([O:43][C:44]1[CH:45]=[C:46]([CH:52]=[C:53]([CH2:55][CH2:56][CH2:57][O:58][CH3:59])[CH:54]=1)[CH2:47][N:48]([CH:49]1[CH2:51][CH2:50]1)[C:33]([C@@H:10]1[C@@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][O:23][C:24]3[C:29]([Cl:30])=[CH:28][C:27]([CH3:31])=[CH:26][C:25]=3[Cl:32])=[CH:16][CH:15]=2)[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1)=[O:35])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:37])[CH3:38]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57956095N-[3-{[tert-Butyl(dimethyl)silyl]oxy}-5-(3-methoxypropyl)benzyl]cyclo-propanamineHCID 59234216(3R,4S)-1-(tert-butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-3-carboxylic acid

Produkt 1

HCID 86639853tert-Butyl (3R,4S)-3-{[[3-{[tert-butyl(dimethyl)silyl]oxy}-5-(3-methoxy-propyl)benzyl](cyclopropyl)amino]carbonyl}-4-{4-[2-(2,6-dichloro-4-methyl-phenoxy)ethoxy]phenyl}piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (3R,4S)-1-(tert-butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-3-carboxylic acid (piperidine acid 1) (1 eq) and N-[3-{[tert-Butyl(dimethyl)silyl]oxy}-5-(3-methoxypropyl)benzyl]cyclo-propanamine (amine 1) (1.8 eq.) in DCM (0.15 M) was added HATU (1.5 eq.) and Hunig's base (3 eq.). After stirring for 18 hr at rt, the reaction was diluted with ether. The organic extract was washed three times with 1 N aqueous HCl, water, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 20% EtOAc in Hex) to afford the title compound as an oil.

Aufarbeitung

  1. extractionThe organic extract
  2. washwas washed three times with 1 N aqueous HCl, water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography (SiO2, 20% EtOAc in Hex)

Quellen und Nachweise

ORD-Eintrag
ord-43dc98af8a2b401194bb63835ec3fb9c
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08076359B2

Notizen zur Reaktion

Wird geladen…