Ammonium Chloride → 1-(Tert-butyl) 3-methyl 4-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)-5,6-dihydropyridine-1,3(2h)-dicarboxylate

HRID 658230Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 658230
[Si:1]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li]CCCC.[CH3:24][O:25][C:26]([C:28]1[CH2:29][N:30]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:31][CH2:32][C:33]=1OS(C(F)(F)F)(=O)=O)=[O:27].[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.CCOC(C)=O>[CH3:24][O:25][C:26]([C:28]1[CH2:29][N:30]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:31][CH2:32][C:33]=1[C:15]1[CH:16]=[CH:17][C:12]([O:11][CH2:10][CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[CH:13][CH:14]=1)=[O:27]

Komponenten

9

Edukt 4

HCID 25517Ammonium ChlorideHCID 150978074-[2-(Tert-butyldimethylsilanyloxy)ethoxy]bromobenzeneHCID 152219361-Tert-butyl 3-methyl 4-(trifluoromethanesulfonyloxy)-1,2,5,6-tetrahydropyridine-1,3-dicarboxylateHCID 178418339Butyllithium

Produkt 1

HCID 684912491-(Tert-butyl) 3-methyl 4-(4-(2-((tert-butyldimethylsilyl)oxy)ethoxy)phenyl)-5,6-dihydropyridine-1,3(2h)-dicarboxylateAusbeute 82,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

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

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a sol. of 4-[2-(tert-butyldimethylsilanyloxy)ethoxy]bromobenzene (WO 03/093267, 7.95 g, 24 mmol) in THF (200 mL) at −78° C. was added BuLi (1.6M in hexane, 17.12 mL, 27.4 mmol). The sol. was stirred at −78° C. for 30 min, then ZnCl2 (1M in THF, 30 mL, 30 mmol) was added. The resulting sol. was allowed to warm to rt, and 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957, 7.79 g, 20 mmol) in THF (20 mL) and Pd(PPh3)4 (0.69 g, 0.60 mmol) were added. The reaction mixture was heated to 50° C. for 1 h, and stirred 16 h at rt. The mixture was cooled to 0° C., and aq. sat. NH4Cl was added. EtOAc was added, and the org. phase was washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 2:8→1:0) yielded the title compound (8.1 g, 82%). LC-MS: tR=1.23 min, ES+: 506.47.

Aufarbeitung

  1. temperatureto warm to rt
  2. temperatureThe reaction mixture was heated to 50° C. for 1 h
  3. stirringstirred 16 h at rt
  4. temperatureThe mixture was cooled to 0° C.
  5. washphase was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvents were removed under reduced pressure
  9. customPurification of the residue by FC (EtOAc/heptane 2:8→1:0)

Quellen und Nachweise

ORD-Eintrag
ord-0f98cd4c79cc43459a5a141e034a4541
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08076359B2

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