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

HRID 1481710Notes

Reaction equation

HRID 1481710 reaction equation
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]

Participants

7

Reactant 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

Product 1

HCID 71281709Methyl 6-(5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrol-2-yl)-5-ethyl-2-methoxynicotinateYield 50.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-b107da78a0504f54bc70f549513f1125
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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