Water → HCID 57447325, compound

HRID 1472206Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[F:11].[CH3:13][N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C([O-])([O-])=O.[K+].[K+].O>CN(C)C=O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([N:17]2[CH2:18][CH2:19][N:14]([CH3:13])[CH2:15][CH2:16]2)=[CH:6][C:5]=1[F:11].[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[N:17]1[CH2:18][CH2:19][N:14]([CH3:13])[CH2:15][CH2:16]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2,4-difluoro-benzoic acid methyl ester (4.5 g, 26.2 mmol), 1-methyl-piperazine (4.36 mL, 39.2 mmol, 1.5 eq.) and K2CO3 (3.62 g, 26.2 mmol, 1 eq.) in N,N-dimethylformamide (10 mL) was stirred at 100° C. for 4 hours. The mixture was then poured into 200 mL of water and extracted with 150 mL of EtOAc. The organic layer was separated, washed with water (100 mL) dried over sodium sulphate and evaporated to dryness. The crude was purified by flash chromatography on silica gel, using a mixture dichloromethane-MeOH-30% NH4OH 95:5:0.5 as eluant, affording 1.65 g of 2-fluoro-4-(4-methyl-piperazin-1-yl)-benzoic acid methyl ester (first eluting, pale yellow solid) and 3.04 g of 4-fluoro-2-(4-methyl-piperazin-1-yl)-benzoic acid methyl ester (second eluting, yellow oil).

Workup

extractionextracted with 150 mL of EtOAc
customThe organic layer was separated
washwashed with water (100 mL)
dry with materialdried over sodium sulphate
customevaporated to dryness
customThe crude was purified by flash chromatography on silica gel

Sources & evidence

ORD record: ord-373dfa9d41e8440c846b1efd0def8a71
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012487B2

Reaction notes

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