Lithium Hydroxide → HCID 66855709, compound

To a solution of 3-(4-fluoro-2-ethylamino-phenyl)-acrylic acid methyl ester (128 mg, 0.57 mmol) in THF (4 mL) and MeOH (2 mL) was added 1 N LiOH (4 mL). The mixture was stirred for 2 hours at room temperature, concentrated under reduced pressure, and then acidified with 3 N HCl. The mixture was diluted with EtOAc, washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give 3-(4-fluoro-2-ethylamino-phenyl)-acrylic acid (88 mg, 73%) after purification by crystallization form EtOAc and hexane. To a mixture of 3-(4-fluoro-2-ethylamino-phenyl)-acrylic acid (40 mg, 0.19 mmol), (R)-[1-(3,5-difluoro-4-methanesulfonylaminophenyl)-ethylamine hydrochloride (55 mg, 0.19 mmol) and N-methylmorpholine (31 μL, 0.28 mmol) in THF (4 mL) was added 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methylmorpholirium chloride hydrate (DMTMM, 58 mg, 0.21 mmol). The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The residue was diluted with EtOAc and water, washed with 2 N HCl and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (4.9 mg, 6%) after purification by column chromatography (EtOAc:hexane=1:10 to 2:1).

1. concentrationconcentrated under reduced pressure
2. additionThe mixture was diluted with EtOAc
3. washwashed with water
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure

ORD record

ord-e08fc4242e104c2b9a3a4ad5787b3efd

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08557872B2