Sodium Bicarbonate → 4-(4-(((2-((Tert-butoxy)carbonylamino)-1-(methoxycarbonyl)ethyl) amino)sulfonyl)-3,5-dimethylphenoxy)butanoic acid

Participants

Reaction Steps

A slurry of H-Dap(Boc)-OMe.HCl (19) (8.0 g, 31.4 mmol) and NaHCO3 (38.6 g, 460 mmol) in 140 mL dioxane/28 mL H2O was cooled to 5° C. with an ice bath. To this slurry was added a solution of the 4-(chlorosulfonyl)-3,5-dimethylphenoxybutanoic acid, 18 (14.0 g 46 mmol) in dioxane (140 mL) dropwise over a period of 75 minutes. After an additional 2 hr the reaction mixture was filtered and the filtrate concentrated in vacuo. To the residue was added water (total volume of 420 mL) and then this was extracted with 75 mL MTBE. The aqueous phase was made acidic (pH=4) using 3 N HCl (aq.) then extracted with EtOAc (300 mL). The EtOAc extract was dried over Na2SO4, filtered and concentrated in vacuo leaving 10.2 g of desired product, 20 (20.9 mmol, 66.5% based on 19, 45% based on 18).

Provenance & Evidence