Lithium Hydroxide → (S)-6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]nicotinic acid

Temperature

50 °C

A mixture of (S)-methyl 6-[(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)amino]nicotinate (53.0 g, 119.5 mmol) was dissolved in methanol (239 ml) and tetrahydrofuran (120 ml) and treated with aqueous lithium hydroxide (120 ml, 239 mmol, 2.0M). An additional aliquot of methanol was added to homogenize the mixture (110 ml, ˜2 ml/g). The reaction was heated to 50° C. for 12 h. The reaction was concentrated in vacuo, and the crude residue was diluted with water (500 ml). The solution was vigorously stirred and slowly acidified with aqueous 1.0M hydrochloric acid (240 ml, to approximately pH 5.0). The precipitated solid was collected by filtration and the remaining solid was dissolved with ethyl acetate and transferred into a separate flask. The crude solid was dried in vacuo and used directly for further transformations.

1. concentrationThe reaction was concentrated in vacuo
2. additionthe crude residue was diluted with water (500 ml)
3. stirringThe solution was vigorously stirred
4. filtrationThe precipitated solid was collected by filtration
5. dissolutionthe remaining solid was dissolved with ethyl acetate
6. customtransferred into a separate flask
7. customThe crude solid was dried in vacuo

ORD record

ord-67f95c18a12a4f529e056d309fc177c3

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809342B2