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

HRID 1481710노트

반응식

HRID 1481710 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 962Water용매2회

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b107da78a0504f54bc70f549513f1125
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409905B2

반응 노트

불러오는 중…