2,3-difluoro-5-iodo-N,N-dimethyl-benzamide → 3-fluoro-2-(4-hydroxy-cyclohexylamino)-5-iodo-N,N-dimethyl-benzamide
Reaction equation
F[C:2]1[C:12]([F:13])=[CH:11][C:10]([I:14])=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].[NH2:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([OH:22])[CH2:18][CH2:17]1>Cl.ClCCl>[F:13][C:12]1[C:2]([NH:15][CH:16]2[CH2:21][CH2:20][CH:19]([OH:22])[CH2:18][CH2:17]2)=[C:3]([CH:9]=[C:10]([I:14])[CH:11]=1)[C:4]([N:6]([CH3:8])[CH3:7])=[O:5]Participants
Procedure
2,3-Difluoro-5-iodo-N,N-dimethyl-benzamide (2.36 g, 7.6 mmol) and trans-4-amino-cyclohexanol (3.5 g, 30 mmol) were stirred at 120° C. for 5 hrs. The resulting solid was dissolved in 1 N hydrochloric acid and dichloromethane. The aqueous layer was extracted with dichloromethane twice. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulfate and concentrated to give 2.8 g (6.84 mmol, 91%) of 3-fluoro-2-(4-hydroxy-cyclohexylamino)-5-iodo-N,N-dimethyl-benzamide as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.45 (dd, J1=12 Hz, J2=2 Hz, 1H), 7.15 (s, 1H), 4.57 (dd, J1=10 Hz, J2=3 Hz, 1H), 4.50 (d, J=4.5 Hz, 1H), 3.33 (m, 1H), 3.02 (m, 1H), 2.94 (bs, 3H), 2.81 (bs, 3H), 1.74 (m, 4H), 1.04-1.24 (m, 4H); MS: m/z 407 [MH+]
Workup
- extractionThe aqueous layer was extracted with dichloromethane twice
- washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
- dry with materialdried over magnesium sulfate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-fbd1cd5b53604a4fa9c8a2282480655a
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08268994B2
Reaction notes
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