Sodium Carbonate → methyl 5-(2-chloro-4-fluorophenyl)-4-methyl-1H-pyrrole-3-carboxylate

HRID 451366Notes

Reaction equation

Br[C:2]1[NH:6][CH:5]=[C:4]([C:7]([O:9][CH3:10])=[O:8])[C:3]=1[CH3:11].[Cl:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C.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]>[Cl:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:2]1[NH:6][CH:5]=[C:4]([C:7]([O:9][CH3:10])=[O:8])[C:3]=1[CH3:11]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of methyl 5-bromo-4-methyl-1H-pyrrole-3-carboxylate (0.63 g, 2.8 mmol), (2-chloro-4-fluorophenyl)boronic acid (1.0 g, 5.7 mmol), Na2CO3 (0.91 g, 8.6 mmol) and palladium tetrakis(triphenylphosphine) (0.17 g, 0.14 mmol) in toluene/water (10:1, 25 ml) was stirred at 110° C. for 9.0 h under N2. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was washed with water and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (6:1 to 1:1 hexane:ethyl acetate) to give the title compound (634 mg, 84%) as a white solid.

Workup

temperatureThe reaction mixture was cooled to room temperature
washThe mixture was washed with water and brine
dry with materialdried over sodium sulfate
concentrationconcentrated on a rotary evaporator
customThe resulting residue was purified by silica-gel column chromatography (6:1 to 1:1 hexane:ethyl acetate)

Sources & evidence

ORD record: ord-89a792b4cf984429928c46ec9715c495
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08487117B2

Reaction notes

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