Diethyl Ether → tert-butyl 2-(3-fluoro-4-((((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methoxy)methyl)phenyl)acetate

Participants

Reaction Conditions

Reaction Steps

A 0.5 M solution of 2-(tert-butyloxy)-2-oxoethylzinc chloride in Et2O (14.6 mL, 7.3 mmol) was added to a mixture of 5-(4-((1R,2R)-2-((4-bromo-2-fluorobenzyloxy)methyl)cyclopropyl)piperidin-1-yl)-3-isopropyl-1,2,4-oxadiazole (Step B product, 1.1 g, 2.43 mmol), Pd2(dba)3 (110 mg, 0.122 mmol), and X-PHOS (116 mg, 0.243 mmol) in anhydrous THF (3 mL). The reaction mixture was stirred and heated at 65° C. overnight. The following morning the mixture was cooled to rt and filtered through a plug of celite, washing with EtOAc. The volatiles were removed under reduced pressure and the residue was loaded onto a silica column (KP-Sil 50 g SNAP column, Biotage system) eluting with a range of 5-45% EtOAc/Hex over 13 CV to give the desired compound (910 mg, 78%). LC/MS (m/z): 488 (M+H)+.

Provenance & Evidence