tert-Butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate → tert-Butyl (3S,9aR)-3-[(3S)-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-6-yl]hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

Participants

Reaction Steps

Intermediates 8E and 8F were prepared in a similar manner as Intermediates 8A and 8B except (3S)-6-Bromo-3-methyl-3,4-dihydro-1H-isochromen-1-one and tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate were used as the starting materials. The cis/trans mixture was purified via MPLC (20-65% EtOAc/Hex). The faster eluting diastereomer was the trans isomer: 8E: 1H NMR (500 MHz; CDCl3): 8.07 (d, J=8.2 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.27 (s, 1H), 4.71 (dd, J=2.0, 10.7 Hz, 1H), 4.68 (m, 1H), 4.0 (bs, 2H), 3.97 (dd, J=3.1, 11.1 Hz, 2H), 3.48 (t, J=10.8 Hz, 1H), 2.99 (m, 4H), 2.74 (d, J=10.5 Hz, 1H), 2.2 (m, 3H), 1.53 (d, J=6.4 Hz, 3H), 1.49 (s, 9H). (M+1)+ 403. 8F: 1H NMR (500 MHz; CDCl3): 8.09 (d, J=8.9 Hz, 1H), 7.53 (d, J=8.3 Hz, 1H), 7.39 (s, 1H), 4.81 (t, J=3.6 Hz, 1H), 4.69 (m, 1H), 3.62 (dd, J=3.0, 11.5 Hz, 1H), 3.42 (m, 1H), 3.24 (dd, J=3.6, 12.1 Hz, 1H), 2.97 (m, 4H), 2.76 (m, 3H), 2.50 (m, 2H), 2.28 (m, 1H), 1.54 (d, J=6.2 Hz, 3H), 1.47 (s, 9H). (M+1)+ 403.

Provenance & Evidence