Triphenylphosphine → N-Trifluoroacetyl-7-methoxy-1-methylene 2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 2389398Notes

Reaction equation

HRID 2389398 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

7

Reactant 3

HCID 11776TriphenylphosphineHCID 517044Potassium AcetateHCID 222927722,2,2-Trifluoro-N-[2-(2-iodo-5-methoxyphenyl)ethyl]acetamide

Product 1

HCID 22292788N-Trifluoroacetyl-7-methoxy-1-methylene 2,3,4,5-tetrahydro-1H-3-benzazepineYield 462.7%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

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) d 7.26 (d, J=8 Hz, 1H), 6.77 (d, J=8 Hz, 1H), 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

  1. temperatureThe product mixture was cooled to 20 C
  2. filtration, filtered
  3. additiondiluted with water (500 mL)
  4. extractionextracted with ether (3×500 mL)
  5. washThe combined organic phases were washed with water (100 mL), brine (100 mL)
  6. dry with materialdried with Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-49adfc650af44dafa2e3f122514ae533
Source dataset
uspto-grants-2012_09
Patent number
US08273734B1

Reaction notes

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