Methanol → 4-(4-Chloro-phenyl)-3,4,5,6-tetrahydro-2H-[4,4']bipyridinyl-1-carboxylic acid tert-butyl ester

HRID 45562

Reaktionsgleichung

Reaktionsgleichung von HRID 45562
[C:1]([O:5][C:6](=[O:14])[N:7]([CH2:11][CH2:12]Cl)[CH2:8][CH2:9]Cl)([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[CH:28]=[CH:27][C:19]([CH2:20][C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)=[CH:18][CH:17]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].CO>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:7]1[CH2:11][CH2:12][C:20]([C:19]2[CH:27]=[CH:28][C:16]([Cl:15])=[CH:17][CH:18]=2)([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)[CH2:9][CH2:8]1)=[O:14])([CH3:4])([CH3:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 887MethanolHCID 781244-(4'-Chlorobenzyl)pyridineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Produkt 1

HCID 593319434-(4-Chloro-phenyl)-3,4,5,6-tetrahydro-2H-[4,4']bipyridinyl-1-carboxylic acid tert-butyl esterAusbeute 0,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Under nitrogen, a solution of bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester* (1.54 g, 6.36 mmol) in toluene (10 mL) was cooled in ice. 4-(4-Chloro-benzyl)-pyridine (1.30 g, 6.36 mmol) was added, followed over two minutes by sodium hexamethyldisilazide solution (10 mL, 20 mmol, 2M in THF). The mixture was stirred at 0° C. for 3.5 hours then allowed to warm to room temperature and stirred for a further 20 hours. Methanol was added then the mixture was concentrated in vacuo. The residue was taken up in ethyl acetate and washed with 1N hydrochloric acid (×3) and brine, dried (MgSO4), filtered and concentrated to afford a residue which was purified by column chromatography (SiO2), eluting with gradient of 2M methanolic ammonia in dichloromethane (1% to 5%). A second purification by column chromatography (SiO2), eluting with 50% ethyl acetate/petrol gave the title compound (16 mg, 0.7%). LCMS (PS-A2) Rt 2.65 min [M+H]+ 373.

Aufarbeitung

  1. temperatureto warm to room temperature
  2. stirringstirred for a further 20 hours
  3. concentrationthe mixture was concentrated in vacuo
  4. washwashed with 1N hydrochloric acid (×3) and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a residue which
  9. customwas purified by column chromatography (SiO2)
  10. washeluting with gradient of 2M methanolic ammonia in dichloromethane (1% to 5%)
  11. customA second purification by column chromatography (SiO2)
  12. washeluting with 50% ethyl acetate/petrol

Quellen und Nachweise

ORD-Eintrag
ord-cbc7dc22ca7f4a038e653523e7fb978d
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541461B2

Verknüpfte Notizen

Wird geladen…