Binap, (A+-)- → 2,4,6-trifluoro-N-methyl-N-[6-(1-t-butoxycarbonyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide

HRID 30216

Reaktionsgleichung

Reaktionsgleichung von HRID 30216
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[O:9])[N:3]=1.[CH3:23][NH:24][C:25](=[O:35])[C:26]1[C:31]([F:32])=[CH:30][C:29]([F:33])=[CH:28][C:27]=1[F:34].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:32][C:31]1[CH:30]=[C:29]([F:33])[CH:28]=[C:27]([F:34])[C:26]=1[C:25]([N:24]([CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[O:9])[N:3]=1)=[O:35]

Komponenten

7

Edukt 4

HCID 634876Binap, (A+-)-2×HCID 179803442,4,6-trifluoro-N-methylbenzamide2×HCID 23676156Sodium t-butoxide2×HCID 866009232-Bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine

Produkt 1

HCID 674431142,4,6-trifluoro-N-methyl-N-[6-(1-t-butoxycarbonyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamideAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator2×HCID 1140TolueneLösungsmittel

Versuchsvorschrift

Heat a mixture of 2-bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine (152 mg, 0.41 mmol), N-methyl-2,4,6-trifluorobenzamide (92.6 mg, 0.49 mmol), Pd2(dba)3 (9.2 mg, 0.01 mmol), BINAP (12.4 mg, 0.02 mmol), sodium t-butoxide (55 mg, 0.57 mmol) in anhydrous toluene (10 mL) at 85° C. for 16 hrs. Cool the reaction to room temperature and add another aliquot of N-methyl-2,4,6-trifluorobenzamide, Pd2(dba)3, BINAP and sodium t-butoxide in the same amount. Re-heat the reaction at 85° C. for 16 more hours. Extract the reaction mixture with ethyl acetate and aqueous NaOH (0.1 N). Collect and dry the organic layers. Concentrate and purify the crude product by chromatography (silica gel, 10% -30% ethyl acetate/hexane) to obtain 2,4,6-trifluoro-N-methyl-N-[6-(1-t-butoxycarbonyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide (86 mg, 44% yield).

Aufarbeitung

  1. temperatureHeat
  2. temperatureCool
  3. customthe reaction to room temperature
  4. customRe-heat the reaction at 85° C. for 16 more hours
  5. extractionExtract the reaction mixture with ethyl acetate and aqueous NaOH (0.1 N)
  6. customCollect
  7. customdry the organic layers
  8. concentrationConcentrate
  9. custompurify the crude product by chromatography (silica gel, 10% -30% ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-8b4a18e651214bd7b36a8a82ca782bce
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07423050B2

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