Ammonium Chloride → 7-{2-[2-(2,6-Dichloro-4-methylphenoxy)ethoxy]thiazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl ester

Participants

Reaction Conditions

Reaction Steps

A cooled (−78° C.) sol. of 2-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]thiazole (3.11 g, 10.2 mmol) in anhydrous THF (90 mL) was treated dropwise with BuLi (1.6 M in hexane; 7.00 mL; 11.2 mmol). After additional stirring at −78° C. for 1 h, ZnCl2 (1M in THF, 12.3 mL, 12.3 mmol) was added dropwise, and the resulting reaction mixture was allowed to warm up to rt for 1.5 h. A sol. of compound Y (4.34 g, 8.18 mmol) and Pd(PPh3)4 (284 mg, 0.246 mmol) in THF (20 mL) was added and the resulting mixture was heated to 50° C. for 1 h. The mixture was cooled to 0° C., and aq. sat. NH4Cl (30 mL) was added. EtOAc (200 mL) was added, and this mixture was successively washed with aq. sat. NH4Cl (150 mL) and brine (150 mL). The org. phase was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane/EtOAc, 3:2) yielded the title compound as a pale yellow solid (5.21 g, 93%). LC-MS: tR=1.19 min, ES+: 684.16.

Provenance & Evidence