Cesium carbonate → HCID 58110358, compound

HRID 238277

Reaction equation

HRID 238277 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8](Br)[S:7][CH:6]=1)=[O:4].C(=O)([O-])[O-].[Cs+].[Cs+].C(OC([N:24]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[N:25]1)=O)(C)(C)C>COCCOC.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8]([C:27]2[CH:28]=[N:24][NH:25][CH:26]=2)[S:7][CH:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 45873035Methyl 5-bromothiophene-3-carboxylate

Product 1

HCID 58110358HCID 58110358, compoundYield 53.5%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

5-Bromo-thiophene-3-carboxylic acid methyl ester (6 g, 27 mmol) was dissolved in a mixture of DME (75 mL), IMS (25 mL) and water (12.5 mL). Caesium carbonate (13.2 g, 40 mmol) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (9.2 g, 31 mmol) were added and the mixture stirred under argon. Palladium tetrakis-(triphenylphosphine) (3.1 g, 2.7 mmol) was then added and the mixture heated at 110° C. for 6 hours. The mixture was allowed to cool to room temperature and then diluted with water. The product was extracted into DCM and washed with brine, then dried over sodium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was triturated with diethyl ether to give the title compound as a pale yellow solid (3.01 g). LCMS m/z 209.1 [M+H]+. R.T.=3.72 min (Analytical Method 4). 1H NMR (400 MHz, d6-DMSO): δ 8.2 (s, 1H), 8.15 (s, 1H), 7.85 (s, 1H), 7.5 (s, 1H), 3.8 (s, 3H).

Workup

  1. temperatureto cool to room temperature
  2. extractionThe product was extracted into DCM
  3. washwashed with brine
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent removed by evaporation under vacuum
  7. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-7cb3435494504c13b0bb5791727fe208
Source dataset
uspto-grants-2014_02
Patent number
US08642621B2

Linked notes

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