Potassium Carbonate → 3-[1-(2-Chloro-phenyl)-ethoxy]-5-pyridin-3-yl-thiophene-2-carboxylic acid methyl ester

HRID 533227Notes

Reaction equation

HRID 533227 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:9]=1[O:10][CH:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])[CH3:12])=[O:4].Br[C:30]1[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)=[CH:8][C:9]=1[O:10][CH:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19])[CH3:12])=[O:4]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 122863-BromopyridineHCID 58970492HCID 58970492, compound

Product 1

HCID 596673583-[1-(2-Chloro-phenyl)-ethoxy]-5-pyridin-3-yl-thiophene-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

3-[1-(2-Chloro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thiophene-2-carboxylic acid methyl ester (150 mg, 0.37 mmol, 1.0 Eq.), 3-bromopyridine (69 mg, 0.44 mmol, 1.2 Eq.) and Pd(PPh3)4 (42 mg, 0.04 mmol, 0.1 Eq.) were dissolved in toluene (1.6 mL) and EtOH (0.4 mL). 2M K2CO3 (0.55 mL, 1.10 mmol, 3.0 Eq) and the reaction heated under microwave conditions at 140° C. for 15 minutes. The reaction was partitioned between EtOAc (10 mL) and water (10 mL) and the aqueous phase extracted with EtOAc (3×10 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (ISCO Companion™, 12 g column, 0-100% EtOAc/petroleum Ether) to give the sub-title compound as am off-white solid (58 mg, 0.16 mmol, 42%); 1H NMR (400 MHz, CDCl3) δ 1.74 (3H, d), 3.93 (3H, s), 5.87 (1H, q), 6.93 (1H, s), 7.25-7.41 (4H, m), 7.68 (1H, dd), 7.72 (1H, dd), 8.58 (1H, dd), 8.78 (1H, d).

Workup

  1. customThe reaction was partitioned between EtOAc (10 mL) and water (10 mL)
  2. extractionthe aqueous phase extracted with EtOAc (3×10 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography (ISCO Companion™, 12 g column, 0-100% EtOAc/petroleum Ether)

Sources & evidence

ORD record
ord-912b67d22dd4454782a75c29c8b12692
Source dataset
uspto-grants-2014_10
Patent number
US08853244B2

Reaction notes

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