Potassium Carbonate → 4-(4-Fluoro-2-methoxycarbonyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1810992Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1F.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:5]2[CH:6]=[CH:7][C:8]([F:10])=[CH:9][C:4]=2[C:3]([O:2][CH3:1])=[O:12])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

Conditions

Temperature: 110 °C

Procedure

2,5-Difluorobenzoic acid methyl ester (25 g, 145 mmol), piperazine-1-carboxylic acid tert-butyl ester (27 g, 145 mmol) and K2CO3 (50 g, 363 mmol) are added to 1,4-dioxane and the mixture is heated to 110° C. for 2 days. The reaction mixture is cooled, inorganic salts filtered through sintered funnel and filtrate is concentrated under reduced pressure. Crude compound is purified by column chromatography (silica-gel, 100-200 mesh, eluent; 5% EtOAc in hexane) to afford desired 4-(4-fluoro-2-methoxycarbonyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester as a syrupy liquid (8.1 g, 16.3%).

Workup

temperatureThe reaction mixture is cooled
filtrationinorganic salts filtered through sintered funnel
concentrationfiltrate is concentrated under reduced pressure
customCrude compound is purified by column chromatography (silica-gel, 100-200 mesh, eluent; 5% EtOAc in hexane)

Sources & evidence

ORD record: ord-10a14e2f983b4080adc37e9673a6527a
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362249B2

Reaction notes

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