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

HRID 1481710ノート

反応式

HRID 1481710 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 962Water溶媒2 回

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-b107da78a0504f54bc70f549513f1125
出典データセット
uspto-grants-2016_08
特許番号
US09409905B2

反応ノート

読み込み中…