Sodium Carbonate → Methyl 5-chloro-4-(1-ethyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate

HRID 1845649Notes

Reaction equation

HRID 1845649 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[S:5][C:6]=1[Cl:7].C([O-])([O-])=O.[Na+].[Na+].[CH2:18]([N:20]1[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=[N:21]1)[CH3:19]>C1COCC1.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]>[Cl:7][C:6]1[S:5][C:4]([C:8]([O:10][CH3:11])=[O:9])=[CH:3][C:2]=1[C:24]1[N:20]([CH2:18][CH3:19])[N:21]=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 532172521-Ethylpyrazole-5-boronic acid, pinacol esterHCID 57826388Methyl 4-bromo-5-chlorothiophene-2-carboxylate

Product 1

HCID 57826590Methyl 5-chloro-4-(1-ethyl-1H-pyrazol-5-yl)-2-thiophenecarboxylateYield 85.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 4-bromo-5-chloro-2-thiophenecarboxylate (300 mg, 1.17 mmol) in THF (2 mL) was added Na2CO3 (2M, 1.76 mL, 3.52 mmol), Pd(dppf)Cl2 (86, 0.117 mmol) and 1-ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (313 mg, 1.41 mmol). The reaction mixture was heated to 80° C. in a sealed tube under N2. After 2 h, the reaction mixture was concentrated under vacuum and purified on silica (EtOAc/Hex, 20-50%) to afford the title compound (0.272 g, 82%) as a light yellow syrup: LC-MS (ES) m/z=271 (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated under vacuum
  2. custompurified on silica (EtOAc/Hex, 20-50%)

Sources & evidence

ORD record
ord-1796fde5ce384de99aac510303bab7c9
Source dataset
uspto-grants-2015_02
Patent number
US08946278B2

Reaction notes

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