Ammonium Chloride → (rac.)-(1R*,5S*)-7-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-9-methyl-3,9-diaza-bicyclo[3.3.1]non-7-ene-3,6-dicarboxylic Acid 3-tert-butyl Ester 6-ethyl Ester

HRID 2428172Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2428172
[Li]CCCC.Br[C:7]1[CH:20]=[CH:19][C:10]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:9][CH:8]=1.[CH2:21]([O:23][C:24]([C:26]1[C@@H:27]2[N:42]([CH3:43])[C@H:31]([CH2:32][C:33]=1OS(C(F)(F)F)(=O)=O)[CH2:30][N:29]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:28]2)=[O:25])[CH3:22].[NH4+].[Cl-]>C1COCC1.[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>[CH2:21]([O:23][C:24]([CH:26]1[C:33]([C:7]2[CH:20]=[CH:19][C:10]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])=[CH:9][CH:8]=2)=[CH:32][C@H:31]2[N:42]([CH3:43])[C@@H:27]1[CH2:28][N:29]([C:44]([O:46][C:47]([CH3:48])([CH3:50])[CH3:49])=[O:45])[CH2:30]2)=[O:25])[CH3:22]

Komponenten

8

Edukt 4

HCID 25517Ammonium ChlorideHCID 4227167(4-Bromophenoxy)(tert-butyl)dimethylsilaneHCID 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 131728968(rac.)-(1R*,5S*)-7-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-9-methyl-3,9-diaza-bicyclo[3.3.1]non-7-ene-3,6-dicarboxylic Acid 3-tert-butyl Ester 6-ethyl EsterAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3007855ZincchlorideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

BuLi (1.6M in hexane, 31.9 mL, 51.0 mmol) was added to a sol. of (4-bromo-phenoxy)-tert-butyl-dimethyl-silane (12.8 g, 44.5 mmol) in THF (150 mL) at −78° C. The mixture was stirred for 60 min at −78° C., and ZnCl2 (1.1M, 50.5 mL, 55.6 mmol) was added. The mixture was allowed to warm to rt, and a sol. of (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 (WO 2003/093267; 17.0 g, 37.1 mmol) in THF (10 mL) and Pd(PPh3)4 (1.07 g, 0.927 mmol) were added. The mixture was stirred at 50° C. for 25 min, and was allowed to cool to rt. Aq. sat. NH4Cl was added, and the mixture was extracted with EtOAc (3×). The combined org. extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 6:4) yielded the title compound (15.9 g, 83%). LC-MS: tR=0.95 min, ES+: 517.25.

Aufarbeitung

  1. temperatureto warm to rt
  2. stirringThe mixture was stirred at 50° C. for 25 min
  3. temperatureto cool to rt
  4. extractionthe mixture was extracted with EtOAc (3×)
  5. dry with materialextracts were dried over Na2SO4
  6. filtrationfiltered
  7. customthe solvents were removed under reduced pressure
  8. customPurification of the residue by FC (EtOAc/heptane 6:4)

Quellen und Nachweise

ORD-Eintrag
ord-3fbf09bb370849cca25ee48ea702dd54
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07968720B2

Notizen zur Reaktion

Wird geladen…