4-Methylmorpholine → (+/-)-3-{4-[2-Cyclohexyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-ethoxy]-3-methyl-benzoylamino}-2-methyl-propionic acid ethyl ester

A solution of (±)-4-[2-cyclohexyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethoxy]-benzoic acid (0.0813 g, 0.174 mmol) in THF (1.7 mL) is treated with 2-chloro-4,6-dimethoxy-[1,3,5]triazine (CDMT, 0.0338 g, 0.193 mmol) and N-methyl morpholine (NMM, 0.020 mL, 0.27 mmol). The mixture is added to a flask containing (±)-3-amino-2-hydroxy-propionic acid ethyl ester (0.0465 g, 0.274 mmol). Additional NMM (0.030 mL, 0.273 mmol) and H2O (0.4 mL) are added and the reaction is stirred overnight. The reaction mixture is dissolved in EtOAc (10 mL) and washed with 0.1 N HCl (2×10 mL), ph=7 phosphate buffer (1×), brine (1×), dried over MgSO4, filtered, and conc. The residue is loaded onto silica gel and eluted with hexanes using a gradient of 10% EtOAc to 60% EtOAc giving (±)-3-{4-[2-cyclohexyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-ethoxy]-3-methyl-benzoylamino}-2-methyl-propionic acid ethyl ester (0.0568 g, 56%) as a white foam. MS (ES): 582.3 [M−H]−.

1. additionThe mixture is added to a flask
2. washwashed with 0.1 N HCl (2×10 mL), ph=7 phosphate buffer (1×), brine (1×)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. washeluted with hexanes using a gradient of 10% EtOAc to 60% EtOAc

ORD-Eintrag

ord-6db01be673ce4679b78a68fb5dfa4e1f

Quelldatensatz

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07989457B2