Potassium Carbonate → Methyl 6-(5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrol-2-yl)-5-ethyl-2-methoxynicotinate

HRID 1481710Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1481710
Cl[C:2]1[C:10]([CH2:11][CH3:12])=[CH:9][C:5]([C:6]([O-:8])=[O:7])=[C:4]([O:13][CH3:14])[N:3]=1.[CH3:15]C([O-])=O.[K+].Br[C:21]1[S:38][C:24]2[N:25]([CH3:37])[C:26]([CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])=[CH:27][C:23]=2[CH:22]=1.C([O-])([O-])=O.[K+].[K+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Si:30]([O:29][CH2:28][C:26]1[N:25]([CH3:37])[C:24]2[S:38][C:21]([C:2]3[C:10]([CH2:11][CH3:12])=[CH:9][C:5]([C:6]([O:8][CH3:15])=[O:7])=[C:4]([O:13][CH3:14])[N:3]=3)=[CH:22][C:23]=2[CH:27]=1)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 712816522-Bromo-5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrroleHCID 1317366566-Chloro-5-ethyl-2-methoxynicotinate

Produkt 1

HCID 71281709Methyl 6-(5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrol-2-yl)-5-ethyl-2-methoxynicotinateAusbeute 50,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Katalysator2×HCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

6-Chloro-5-ethyl-2-methoxynicotinate (0.575 g, 2.50 mmol), bis(pinacolato) diborate (0.800 g, 315 mmol), Pd(dppf)Cl2 (73.0 mg, 0.1 mmol, 4 mol %), and KOAc (0.750 g, 7.64 mmol) were mixed together in a heat-gun dried vial. The vial was vacuumed and backfilled with argon before dioxane (10 mL) was added. Mixture was heated at 100° C. overnight then was cooled to room temperature. 2-Bromo-5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrole (0.900 g, 2.50 mmol), fresh Pd(dppf)Cl2 (73.0 mg, 0.1 mmol, 4 mol %), K2CO3 (1.05 g, 7.60 mmol) and H2O (2.50 mL) were added and reaction vial was resealed under argon and mixture was heated at 100° C. for 2 h. Mixture was then cooled to room temperature, diluted with H2O (15 mL) and product was extracted with DCM (3×20 mL). Combined organics were washed with NaCl (aqueous saturated, 15 mL) and dried over Na2SO4. After concentration of the solvent the residue was purified by column chromatography (EtOAc/hexanes, 0-15% gradient). Methyl 6-(5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrol-2-yl)-5-ethyl-2-methoxynicotinate (0.594 g) was obtained as oil and was taken directly into the next step.

Aufarbeitung

  1. customdried vial
  2. additionwas added
  3. temperaturethen was cooled to room temperature
  4. customreaction
  5. temperaturemixture was heated at 100° C. for 2 h
  6. temperatureMixture was then cooled to room temperature
  7. extractionwas extracted with DCM (3×20 mL)
  8. washCombined organics were washed with NaCl (aqueous saturated, 15 mL)
  9. dry with materialdried over Na2SO4
  10. customAfter concentration of the solvent the residue was purified by column chromatography (EtOAc/hexanes, 0-15% gradient)

Quellen und Nachweise

ORD-Eintrag
ord-b107da78a0504f54bc70f549513f1125
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409905B2

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