HCID 15342962, Verbindung → (rac.)-(1R*,5S*)-7-{4-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-phenyl}-9-methyl-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl ester

HRID 1715449Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1715449
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:4][CH:3]=1.[Li]CCCC.[CH2:24]([O:26][C:27]([C:29]1[C@@H:30]2[N:45]([CH3:46])[C@H:34]([CH2:35][C:36]=1OS(C(F)(F)F)(=O)=O)[CH2:33][N:32]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:31]2)=[O:28])[CH3:25]>C1COCC1.CCOC(C)=O.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:24]([O:26][C:27]([C:29]1[C@@H:30]2[N:45]([CH3:46])[C@H:34]([CH2:35][C:36]=1[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:4][CH:3]=1)[CH2:33][N:32]([C:47]([O:49][C:50]([CH3:51])([CH3:53])[CH3:52])=[O:48])[CH2:31]2)=[O:28])[CH3:25]

Komponenten

8

Edukt 3

HCID 15342962HCID 15342962, VerbindungHCID 44158352(rac.)-(1R*,5S*)-9-Methyl-7-trifluoromethanesulfonyloxy-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl esterHCID 178418339Butyllithium

Produkt 1

HCID 44158058(rac.)-(1R*,5S*)-7-{4-[3-(tert-Butyl-dimethyl-silanyloxy)-propyl]-phenyl}-9-methyl-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3007855ZincchlorideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A sol. of [3-(4-bromo-phenyl)-propoxy]-tert-butyl-dimethyl-silane (102.1 g, 310 mmol) in THF (1.50 L) under nitrogen is cooled to −78° C. BuLi (1.5M in hexane, 212 mL, 318 mmol) is added. After 30 min, ZnCl2 (1M in THF, 465 mL, 465 mmol) is added. The mixture is allowed to warm up to rt. (rac.)-(1R*,5S*)-9-Methyl-7-trifluoromethanesulfonyloxy-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl ester (83.6 g, 155 mmol) in THF (100 mL) and then Pd(PPh3)4 (4.48 g, 3.87 mmol) are added. The mixture is heated to reflux for 30 min, and allowed to cool to rt. The mixture is diluted with EtOAc and washed with aq. 1M NaOH (1×). The org. extracts are dried over MgSO4, filtered, and the solvents are removed under reduced pressure. Purification of the residue by FC (MeOH/CH2Cl2 1:49→1:24→3:47→2:23) yields the title compound (88.6 g, virtually quantitative). LC-MS: tR=0.98 min; ES+: 559.24.

Aufarbeitung

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 30 min
  3. temperatureto cool to rt
  4. washwashed with aq. 1M NaOH (1×)
  5. dry with materialextracts are dried over MgSO4
  6. filtrationfiltered
  7. customthe solvents are removed under reduced pressure
  8. customPurification of the residue by FC (MeOH/CH2Cl2 1:49→1:24→3:47→2:23)

Quellen und Nachweise

ORD-Eintrag
ord-012ed2ba32de4cd3b46123a9bb22d2a4
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07799805B2

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