Methanol → 4-{[({1-[4-(Trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)amino]carbonyl}benzoic acid

HRID 2093631Notes

Reaction equation

[F:1][C:2]([F:30])([F:29])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][NH:16][C:17]([C:19]3[CH:28]=[CH:27][C:22]([C:23]([O:25]C)=[O:24])=[CH:21][CH:20]=3)=[O:18])[CH2:11][CH2:10]2)[N:4]=1.CO.O.[OH-].[Li+]>O1CCCC1>[F:29][C:2]([F:1])([F:30])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH2:10][CH2:11][CH:12]([CH2:15][NH:16][C:17]([C:19]3[CH:28]=[CH:27][C:22]([C:23]([OH:25])=[O:24])=[CH:21][CH:20]=3)=[O:18])[CH2:13][CH2:14]2)[N:4]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Methyl 4-{[({1-[4-(trifluoromethyl)pyrimidin-2-yl]piperidin-4-yl}methyl)amino]carbonyl}benzoate was dissolved in 24 ml of tetrahydrofuran, 23 ml of methanol, and 23 ml of water. To this solution was added lithium hydroxide (817 mg) and the mixture was stirred at 50° C. for 1.25 h. The solvents were removed in vacuo and the residue was taken up in 1 N HCl (70 ml) and 70 ml of ethyl acetate. The mixture was sonicated until the solid residue mostly dissolved in the ethyl acetate. The two phases were separated, and any remaining product in the aqueous layer was extracted out with ethyl acetate (70 ml). The organic layers were combined, washed with brine (20 ml), and concentrated in vacuo to yield the title compound (1.09 g, 81%). Mass spectrum (ESI) 409.1 (M+1).

Workup

customThe solvents were removed in vacuo
customThe mixture was sonicated until the solid residue
dissolutionmostly dissolved in the ethyl acetate
customThe two phases were separated
extractionany remaining product in the aqueous layer was extracted out with ethyl acetate (70 ml)
washwashed with brine (20 ml)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-b397b774bcaf4745924adeb01956c064
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445480B2

Reaction notes

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