Methyl 3-amino-4-fluorobenzoate → 3-Amino-N-(2-(2,6-cis-dimethylpiperidin-1-yl)ethyl)-4-fluorobenzamide

HRID 1521343Notes

Reaction equation

[Cl-].[CH3:2][C@H:3]1[CH2:8][CH2:7][CH2:6][C@@H:5]([CH3:9])[N:4]1[CH2:10][CH2:11][NH3+:12].[NH2:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1[F:24])[C:17](OC)=[O:18]>C1COCC1>[NH2:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1[F:24])[C:17]([NH:12][CH2:11][CH2:10][N:4]1[C@H:5]([CH3:9])[CH2:6][CH2:7][CH2:8][C@@H:3]1[CH3:2])=[O:18]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture comprising 2-(2,6-cis-dimethylpiperidin-1-yl)ethanaminium chloride (4 g, 20.75 mmol) and methyl 3-amino-4-fluorobenzoate (3.51 g, 20.75 mmol) in THF (50 ml) was treated with TBD (2.89 g, 20.75 mmol) and stirred at 80° C. for 16 hrs. A further portion of methyl 3-amino-4-fluoro benzoate (1 g) and TBD (0.5 g) were added and heating continued for 24 hrs. The resulting mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate. The mixture was extracted once with ethyl acetate and once with chloroform. The combined organic layers were dried (MgSO4), filtered and evaporated to dryness. Purification of the residue by chromatography on silica eluting with 0-20% MeOH in DCM afforded the title compound;

Workup

temperatureheating
waitcontinued for 24 hrs
customThe resulting mixture was partitioned between ethyl acetate and aqueous sodium bicarbonate
extractionThe mixture was extracted once with ethyl acetate and once with chloroform
dry with materialThe combined organic layers were dried (MgSO4)
filtrationfiltered
customevaporated to dryness
customPurification of the residue by chromatography on silica eluting with 0-20% MeOH in DCM

Sources & evidence

ORD record: ord-ad35993110bd4bea81ffe90a95e1a147
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073921B2

Reaction notes

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