Triphenylphosphine → N-Trifluoroacetyl-7-methoxy-1-methylene 2,3,4,5-tetrahydro-1H-3-benzazepine
Reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]([NH:5][CH2:6][CH2:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:9]=1I)=[O:4].CC([O-])=O.[K+].[CH:24]1[CH:29]=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=C[CH:25]=1>CN(C)C=O.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].CC([O-])=O.CC([O-])=O.[Pd+2]>[F:1][C:2]([F:18])([F:17])[C:3]([N:5]1[CH2:29][C:24](=[CH2:25])[C:9]2[CH:10]=[CH:11][C:12]([O:14][CH3:15])=[CH:13][C:8]=2[CH2:7][CH2:6]1)=[O:4]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 90 °C
Procedure
A solution of N-allyl, N-trifluoroacetyl-2-iodo-5-methoxyphenethylamine (20.5 g, 50 mmol) in dimethylformamide (250 mL) is treated with KOAc (14.6 g, 149 mmol), n-Bu4NBr (16.0 g, 50 mmol), PPh3 (1.3 g, 5.0 mmol), Pd(OAc)2 (0.56 g, 2.5 mmol) and stirred overnight at 90° C. The product mixture was cooled to 20° C., filtered, diluted with water (500 mL) and extracted with ether (3×500 mL). The combined organic phases were washed with water (100 mL), brine (100 mL), dried with Na2SO4 and concentrated. Flash chromatography (10% EtOAc in hexane, silica) resulted in 6.6 g of a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.26 (d, J=8 Hz, 1H), 6.77 (d, J=8 Hz, 1 H), 6.66 (s, 1H), 5.34-5.19 (m, 2H), 4.40 (m, 2H), 3.83 (m, 2H), 3.80 (s, 3H), 3.00 (m, 2H). MS calculated for C14H14F3NO2+H: 285, observed: 285.
Workup
- temperatureThe product mixture was cooled to 20° C.
- filtrationfiltered
- additiondiluted with water (500 mL)
- extractionextracted with ether (3×500 mL)
- washThe combined organic phases were washed with water (100 mL), brine (100 mL)
- dry with materialdried with Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-1d3eec452edb40a8810f9a4b7b9a95a1
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08153621B2
Reaction notes
Loading…