5-Aminoisophthalic acid monomethyl ester synthesis

Yield: 92%

Reaction Conditions:

with hydrogen;palladium dihydroxide in methanol under 2585.81 Torr; for 5 h;

Steps:

14.1
EXAMPLE 14 Methyl 5-((lR,2S)-2-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine- l-carbonyl)cyclohexylcarbamoyl)biphenyl-3-carboxylateStep 1 : Preparation of 3-amino-5-(methoxycarbonyl)benzoic acid[00142] 20% Pd(OH)₂ (0.50 g) was carefully wetted down under argon with methanol (5 mL) and then 3-(methoxycarbonyl)-5-nitrobenzoic acid (5.00 g, 22.2 mmol) in methanol (20 mL) was added. The mixture was then hydrogenated on a Parr Shaker apparatus for 5 hours at 50 psi. Under argon, the reaction was carefully filtered through a fiberglass filter paper. The filtrate was concentrated to give 3- amino-5-(methoxycarbonyl)benzoic acid (4.0 g, 20.5 mmol, 92% yield) of off-white solids as product. MS found: (M - H)⁺ = 194.

References:

BRISTOL-MYERS SQUIBB COMPANY WO2009/15166, 2009, A1 Location in patent:Page/Page column 87