N-(4-Bromo-2-fluoro-benzyl)-2-methoxy-4-methylsulfanyl-benzamide → N-(4-bromo-2-fluoro-benzyl)-2-hydroxy-4-methylsulfanyl-benzamide

HRID 2229537Notes

Reaction equation

[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8](=[O:19])[C:9]2[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][C:10]=2[O:17]C)=[C:4]([F:22])[CH:3]=1>Br.C(O)(=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:21]=[CH:20][C:5]([CH2:6][NH:7][C:8](=[O:19])[C:9]2[CH:14]=[CH:13][C:12]([S:15][CH3:16])=[CH:11][C:10]=2[OH:17])=[C:4]([F:22])[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of N-(4-bromo-2-fluoro-benzyl)-2-methoxy-4-methylsulfanyl-benzamide (11g crude, from step 1) was dissolved in a 25% HBr in glacial acetic acid solution (400 mL) and heated to 100° C. for 4 h. The solution was diluted with ethyl acetate (750 mL) and washed with saturated NaCl (500 mL). The organic layer was dried over MgSO4, filtered and concentrated. Purification by MPLC (10-100% ethyl acetate in heptane, 23 mL/min, 75 min) gave N-(4-bromo-2-fluoro-benzyl)-2-hydroxy-4-methylsulfanyl-benzamide (5.0 g, 50%). Rf 0.57 (40% ethyl acetate in heptane); 1H NMR (DMSO-d6 300 MHz) δ 12.57 (s, 1H), 9.22 (t, J=5.4 Hz, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.52 (dd, J1=9.8 Hz, J2=1.7 Hz, 1H), 7.40-7.27 (m, 2H), 6.77-6.71 (m, 2H), 4.46 (d, J=5.7 Hz, 2H), 2.46 (5, 3H).

Workup

washwashed with saturated NaCl (500 mL)
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated
customPurification by MPLC (10-100% ethyl acetate in heptane, 23 mL/min, 75 min)

Sources & evidence

ORD record: ord-31573793b44047ddb5d6815d5601aa8b
Source dataset: uspto-grants-2002_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06420426B1

Reaction notes

Loading…