Hydrochloric Acid → HCID 57506778, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 170 mg (RS)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-[(R)-tetrahydro-furan-3-yloxy]-phenyl]-acetic acid ethyl ester hydrochloride described in example 3.8 in 5 ml THF was cooled to 0° C. and treated with 1.8 ml 1N LiOH solution. The mixture was stirred for 2 hrs at 0° C., then neutralized with 1N HCl. The precipitate was filtered off and washed with H2O and Et2O to yield 129 mg of (RS)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-[(R)-tetrahydro-furan-3-yloxy]-phenyl]-acetic acid as an off-white solid. This isomeric mixture was separated into the diastereomers by preparative HPLC on a chiral stationary phase (Chiralpak AD) using heptane/isopropanol/trifluoroacetic acid (75:25:0.2) as a mobile phase to give, after neutralization, (R)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-[(R)-tetrahydro-furan-3-yloxy]-phenyl]-acetic acid and (S)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-3-(R)-tetrahydro-furan-3-yloxy]-phenyl]-acetic acid as off-white solids.

Provenance & Evidence