Cesium carbonate → 3-tert-Butoxycarbonylamino-5-(5-fluoropyridin-2-yl)thiophene-2-carboxylic acid methyl ester

HRID 532424Notes

Reaction equation

HRID 532424 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](Br)=[CH:8][C:9]=1[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].Br[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][N:21]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][N:21]=2)=[CH:8][C:9]=1[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

10

Reactant 5

HCID 10796Cesium carbonateHCID 2733548Bis(pinacolato)diboraneHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 27831712-Bromo-5-fluoropyridineHCID 57356848Methyl 5-bromo-3-((tert-butoxycarbonyl)amino)thiophene-2-carboxylate

Product 1

HCID 689429283-tert-Butoxycarbonylamino-5-(5-fluoropyridin-2-yl)thiophene-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

Palladium(II) acetate (20 mg) was added to a solution of 5-bromo-3-tert-butoxycarbonylaminothiophene-2-carboxylic acid methyl ester (300 mg), 2-bromo-5-fluoropyridine (235.5 mg), bis(pinacolato)diboron (462.2 mg), tri-t-butylphosphonium tetrafluoroborate (77.64 mg) and cesium carbonate (871.9 mg) in dioxane/water (6 mL/1.5 mL). The solution was heated at 90° C. for 3 h. The reaction solution was then mixed with ethyl acetate and water. The aqueous phase was extracted several times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The crude product was purified by preparative HPLC. The product with the molecular weight of 352.39 (C16H17FN2O4S) was obtained in this way; MS (ESI): 353 (M+H+).

Workup

  1. extractionThe aqueous phase was extracted several times with ethyl acetate
  2. dry with materialThe combined organic phases were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by preparative HPLC
  5. customThe product with the molecular weight of 352.39 (C16H17FN2O4S) was obtained in this way

Sources & evidence

ORD record
ord-d5be4c950e28456f942ec3c359c27ca3
Source dataset
uspto-grants-2014_10
Patent number
US08853208B2

Reaction notes

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