Methyl 3-(4-((tert-butoxycarbonylaMino)Methyl)phenylsulfonyl)propanoate synthesis

Yield:1362160-41-5 94%

Reaction Conditions:

with Oxone in water;acetonitrile at 20; for 2.5 h;

Steps:

2O.c

c. methyl 3-(4-((tert- butoxycarbonylamino)methyl)phenylsulfonyl)propanoate:A 500-mL RBF equipped with a magnetic stir bar was charged with OXONE (23.61 g, 38.4 mmol) and Water (Ratio: 1.822, Volume: 82 ml). The mixture was stirred at rt for 5 min in order to dissolve the Oxone. Next, a solution of methyl 3- (4-((tert-butoxycarbonylamino)methyl)phenylthio)propanoate (5.0 g, 15.36 mmol) in Acetonitrile (Ratio: 1.000, Volume: 45 ml) was added at rt with rapid stirring. The mixture was stirred at rt. After 2.5 h, an aliquot was removed, worked up, and analyzed by 1H NMR, which confirmed complete conversion to sulfone. LCMS also looked good. The reaction mixture was then extracted with EtOAc (100 mL). This extract was concentrated under reduced pressure. The aqueous layer was re-extracted once with fresh EtOAc. This extract was combined with the first, concentrated extract. The combined solution was washed twice with half-saturated brine (2 x 50 mL) and concentrated under reduced pressure to afford methyl 3 -(4-((tert-butoxycarbonylamino)methyl)phenylsulfonyl)propanoate (5.17 g, 14.46 mmol, 94 % yield) as a white solid.1H NMR (400 MHz, CDC1₃): δ 7.86 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 5.03 (br s, 1H), 4.41 (d, J = 6.2 Hz, 2H), 3.64 (s, 3H), 3.41 (t, J = 7.7 Hz, 2H), 2.74 (t, J = 7.8 Hz, 2H), 1.46 (s, 9H) ppm.ESMS: 380.07 (M+Na)

References:

WO2012/31197,2012,A1 Location in patent:Page/Page column 411-412