Pyridine → 3-(2,2-Difluoro-propyl)-7-methoxy-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine
Reaction equation
[F:1][C:2]([F:6])([CH3:5])[CH2:3]O.N1C=CC=CC=1.C(#N)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[CH3:37][O:38][C:39]1[C:49]([N+:50]([O-:52])=[O:51])=[CH:48][C:42]2[CH2:43][CH2:44][NH:45][CH2:46][CH2:47][C:41]=2[CH:40]=1>>[F:1][C:2]([F:6])([CH3:5])[CH2:3][N:45]1[CH2:46][CH2:47][C:41]2[CH:40]=[C:39]([O:38][CH3:37])[C:49]([N+:50]([O-:52])=[O:51])=[CH:48][C:42]=2[CH2:43][CH2:44]1Participants
Reactant 6
Product 1
Procedure
To mixture of 2,2-Difluoro-propan-1-ol (0.26 g, 0.0027 mol) and Pyridine (0.27 mL, 0.0034-mol) in Acetonitrile (25 mL, 0.48 mol) at 0-5° C. was added dropwise Trifluoromethanesulfonic anhydride (0.48 mL, 0.0028 mol). The mixture was stirred for 30 minutes then Potassium carbonate (0.37 g, 0.0027 mol) and 7-Methoxy-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.30 g, 0.0013 mol) were added. The reaction mixture was warmed to room temperature then heated to 50° C. for 18 hours. The mixture was evaporated. The residue was dissolved in dichloromethane (50 mL) and washed with water (50 mL), dried over magnesium sulfate, filtered and evaporated. The material was purified via silica gel chromatography using 0%→10% Methanol:Dichloromethane solvent gradient. 3-(2,2-Difluoro-propyl)-7-methoxy-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine isolated as a yellow solid (0.316 g, 78%).
Workup
- temperaturethen heated to 50° C. for 18 hours
- customThe mixture was evaporated
- dissolutionThe residue was dissolved in dichloromethane (50 mL)
- washwashed with water (50 mL)
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- customevaporated
- customThe material was purified via silica gel chromatography
Sources & evidence
- ORD record
- ord-666be0057fd949c6a8bd547b1c616ae9
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08148391B2
Reaction notes
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