Tetrabutylammonium Fluoride → (S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid methyl ester

Participants

Reaction Steps

A solution of (S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (3.01 g, 5.66 mmol) in tetrahydrofuran/methanol (1:1, 60 mL) was stirred at 0° C. Tetra-n-butylammonium fluoride (1 M in tetrahydrofuran, 11.3 mL, 11.3 mmol) was added and the reaction mixture was stirred at room temperature for 22 h. The solvent was removed in vacuo and the residue was purified by silica gel chromatography using a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 1:1 afford the title compound (2.14 g, 91%) as a white foam. 1H NMR (300 MHz, CDCl3) δ □0.91 (d, J=6.9 Hz, 3H), 0.95 (d, J=6.9 Hz, 3H), 1.32 (d, J=6.9 Hz, 3H), 1.46 (s, 9H), 1.61-2.17 (m, 6H), 2.80-2.88 (m, 1H), 3.47-3.58 (m, 1H), 3.73-3.78 (s, 3H), 3.94-4.02 (m, 1H), 4.33-4.38 (m, 1H), 5.13 (d, J=8.3 Hz, 1H), 5.27-5.37 (m, 1H), 6.75 (d, J=7.6 Hz, 1H). LCMS (m/z) 415.1 [M+H], Tr=3.17 min.

Provenance & Evidence