2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]thiazole → 7-{2-[2-(tert-Butyldimethylsilanyloxy)ethoxymethyl]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

BuLi (1.6 M in hexane, 5.70 mL, 9.05 mmol) was added dropwise to a cooled (−78° C.) solution of 2-[2-(tert-butyldimethylsilanyloxy)ethoxymethyl]thiazole (1.900 g, 6.786 mmol) in THF (15 mL). 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 removed, and the reaction mixture was stirred for 1 h at rt. A sol. of compound Y (2.00 g, 3.77 mmol) in THF (5 mL) was added dropwise, followed by Pd(PPh3)4 (136 mg, 0.109 mmol). The reaction mixture was stirred at rt for 2 h, partitioned between EtOAc and aq. 1M NaOH, and the layers were separated. The aq. layer was extracted with EtOAc. The combined org. extracts were washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane/EtOAc 7/3) yielded the title compound (1.60 g, 65%) as an orange oil. LC-MS: tR=1.19 min, ES+: 654.33.

Provenance & Evidence