Triethylamine → 2-{2-{[tert-butyl(dimethylsilyl)oxy}-1-[(tert-butylsulfinyl)amino]ethyl}-5-chlorobenzyl)-1-[(9-hydroxy-9H-fluoren-9-yl)carbonyl]-L-prolinamide

Participants

Reaction Steps

A mixture of diastereomer A of N-(1-[2-(aminomethyl)-4-chlorophenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-methylpropane-2-sulfinamide (from the previous step, 67 mg, 0.16 mmol, 1.07 eq), 1-[(9-hydroxy-9H-fluoren-9-yl)carbonyl]-L-proline (48 mg, 0.15 mmol, 1.0 eq (43 mg, 0.22 mmol, 1.5 eq), triethylamine (22 μL, 0.16 mmol, 1.07 eq) and HOAt (10 mg, 0.08 mmol, 0.5 eq) in anhydrous DMF (1 mL) was stirred at room temperature overnight. Most of the DMF was removed in vacuo and the residue was purified by silica gel chromatography (isocratic elution, 1:1 EtOAc:hexanes) to afford diastereomer A of N-(2-{2-{[tert-butyl(dimethylsilyl)oxy}-1-[(tert-butylsulfinyl)amino]ethyl}-5-chlorobenzyl)-1-[(9-hydroxy-9H-fluoren-9-yl)carbonyl]-L-prolinamide as a white solid (66 mg, 61%). 1H NMR (400 MHz, CDCl3): δ 7.66-7.64 (m, 2H), 7.44-7.00 (m, 9H), 5.91 (m, 1H), 4.71-4.58 (m, 3H), 4.40 (m, 1H), 4.35 (br s, 1H), 3.75 (dd, J=4.4, 10.3 Hz, 1H), 3.67 (apparent t, J=9.7 Hz, 1H), 2.38-2.28 (m, 2H), 2.02 (m, 1H), 1.81 (m, 1H), 1.65 (m, 1H), 1.45 (m, 1H), 1.23 (s, 9H), 0.91 (s, 9H), 0.08 (s, 3H), 0.00 (s, 3H). LCMS RT=3.05 min, (M+H)=724.6. Diastereomer B of the amine (17 mg from previous step) was coupled and purified under similar conditions to afford diastereomer B of N-(2-{2-{[tert-butyl(dimethylsilyl)oxy}-1-[(tert-butylsulfinyl)amino]ethyl}-5-chlorobenzyl)-1-[(9-hydroxy-9H-fluoren-9-yl)carbonyl]-L-prolinamide a a pale yellow oil (20 mg) which still contained traces of triphenylphosphine oxide from the previous step. LCMS RT=3.01 min, (M+H)=724.6.

Provenance & Evidence