HCID 15024522, compound → HCID 15870352, compound

Participants

Reaction Conditions

Reaction Steps

A solution containing about 260 mg of compound 7 and 91.5 mg of LiOH monohydrate in 7.5 ml of THF/H2O (2:1) was stirred at 22° C. for about 3 hours. The organic solvent was evaporated and the aqueous solution was extracted with Et2O (2×10 ml) and then acidified to a pH of less than 1 with 1 N HCl. The mixture was extracted again with Et2O (3×10 ml) and the combined organic extracts were dried over Na2SO4 and evaporated to yield about 240 mg of Boc-Tyr(OBn)-Aib-OH. A solution containing about 200 mg of Boc-Tyr(OBn)-Aib-OH in 10 ml of dry CH3CN was treated at 0° C. with 95 mg of DCC and stirred for about 2 hours. After filtration through florosil, the solution was evaporated to dryness. The resulting crude product (8) was dissolved in 2 ml of dry THF and added at -78° C. to a mixture of 130 mg of compound 4 and 165 μM of a 1.5 M solution of N-BuLi in hexanes in 4 ml of dry THF. After addition of about 13 mg of DMAP, the cold bath was removed and the reaction mixture stirred at 22° C. for about 2 hours. The solvent was evaporated and 4 ml of water added. After extraction with CH2Cl2 (3×10 ml), the combined organic layers were dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography on SiO2 (EtOAc/hexanes, 1:1) to yield about 285 mg of compound 9.

Provenance & Evidence