2-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazole → 7-{2-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-5-yl}-3,9-diaza-bicyclo[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

BuLi (1.6 M in hexane, 5.7 mL, 9.1 mmol) was added dropwise to a sol. of 2-[3-(tert-butyldimethylsilanyloxy)propyl]thiazole (1.80 g, 6.79 mmol) in THF (15 mL) at −78° C. The reaction mixture was stirred at −78° C. for 1 h, and ZnCl2 (1M in THF, 11.3 mL, 11.3 mmol) was added dropwise at −78° C. The cooling bath was then removed and the reaction stirred for 1 h while warming up to rt. A sol. of compound Y (2.00 g, 3.77 mmol) in THF (5 mL) was added dropwise, followed by Pd(PPh3)4 (126 mg, 0.109 mmol). The reaction mixture was stirred at rt for 2 h, then partitioned between EtOAc and aq. 1M NaOH, and the layers were separated. The aq. layer was extracted with EtOAc. The combined org. layers were washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification by FC (heptane/EtOAc= 7/3) yielded the title compound (1.75 g, 73%). LC-MS: tR=1.20 min, ES+: 638.35.

Provenance & Evidence