Hydrochloric Acid → (4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-cyclohexyl)-acetic acid

Temperature

60 °C

Add 5 N sodium hydroxide solution (2 mL) to a solution of (4-{5-[(3,5-bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-cyclohexyl)-acetic acid methyl ester (63 mg, 0.088 mmol) in methanol (5 mL) and heat at 60° C. for 4 h. After the reaction cools to room temperature, acidify to pH 4 with 2 N hydrochloric acid solution and extract the aqueous mixture with ethyl acetate (3×10 mL). Wash the organic layer with water and brine (10 mL each). Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure to provide the title compound as an off-white solid (58 mg, 95%). 1H NMR (CDCl3, 300 MHz) δ 0.78-2.45 (m, 22H), 2.63-3.10 (m, 4H), 4.61-4.82 (m, 3H), 5.12-5.19 (m, 1H), 6.89 (s, 1H), 7.12-7.33 (m, 2H), 7.62-7.81 (m, 3H); ESI MS m/z 706 [C34H36F9N3O3+H]+; HPLC 96.3%, tR 18.9 min.

1. customcools to room temperature
2. extractionextract the aqueous mixture with ethyl acetate (3×10 mL)
3. washWash the organic layer with water and brine (10 mL each)
4. dry with materialDry the organic layer over anhydrous sodium sulfate
5. filtrationfilter
6. customremove the solvent under reduced pressure

ORD record

ord-fda91d91c5e74648b678bc9c306d7f66

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07786108B2