Yield:113474-25-2 83%

Reaction Conditions:

with hydrogen;acetic acid;Rh/Al₂O₃ in methanol at 0 - 25; under 2844.39 Torr;

Steps:

2.1

Intermediate 24cis-9-Amino-7,7-difluoro-2-(3-fluoro-phenyl)-2-aza-spiro[4.5]decan-1-one Intermediate 24 was prepared via the process of Scheme 6, supra, as follows:Step 15-Hydroxy-cyclohexane-1,3-dicarboxylic acid dimethyl ester To a solution of dimethyl-5-hydroxyisophthalate (3.50 g, 16.6 mmol) in methanol (60.0 mL) was added 5% rhodium on alumina (0.80 g) at 0° C., followed by acetic acid (0.60 mL, 10.6 mmol). The reaction mixture was shaken under hydrogen (55 psi) at room temperature overnight and then filtered through Celite and concentrated under reduced pressure. The residue was purified by CombiFlash system (12 g silica gel cartridge; gradient: 0 to 50% ethyl acetate in DCM over 30 min) to give 3.00 g (83%) of the title compound, 5-hydroxy-cyclohexane-1,3-dicarboxylic acid dimethyl ester. ¹H NMR (400 MHz, CDCl₃): δ 3.56-3.78 (m, 7H), 2.15-2.51 (m, 5H), 1.25-1.66 (m, 3H).

References:

US2011/98299,2011,A1 Location in patent:Page/Page column 40