4-Bromoaniline → 2-(5-Bromo-pyridin-2-yl)-5-chloro-pentanoic acid (4-bromo-phenyl)-amide
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH2:12][CH2:13][CH2:14][Cl:15])[C:9]([OH:11])=O)=[N:6][CH:7]=1.CCN(CC)CC.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Br:47][C:48]1[CH:53]=[CH:52][C:51]([NH2:54])=[CH:50][CH:49]=1>C(Cl)Cl>[Br:47][C:48]1[CH:53]=[CH:52][C:51]([NH:54][C:9](=[O:11])[CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=2)[CH2:12][CH2:13][CH2:14][Cl:15])=[CH:50][CH:49]=1Participants
Procedure
To a solution of 2-(5-Bromo-pyridin-2-yl)-5-chloro-pentanoic acid (1.9 g, 6.5 mmol), Et3N (3.6 mL, 26 mmol), and Pybrop (6 g, 13 mmol) in CH2Cl2 (30 mL) was added 4-bromo-phenylamine (1.45 g, 8.45 mmol). This mixture was stirred overnight at room temperature and then evaporated. The mixture was redissolved in EtOAc (40 mL) and washed with 2N HCl (20 mL×3), brine, 5% NaHCO3 (20 mL×3), brine, dried with Na2SO4, filtered and evaporated. The residue was purified by column chromatography on silica gel using hexane/EtOAc to give a white solid (1.63 g, 56% for two steps). MS: calc'd 444 (MH+), exp 444 (MH+). 1H NMR (400 MHz, CDCl3-d) 9.65 (broad s, 1H), 8.72 (d, 1H, J=2.0 Hz), 8.06 (d, 1H, J=8.4 Hz), 7.53-7.41 (m, 4H), 4.18-4.08 (m, 1H), 3.66-3.54 (m, 2H), 2.45-2.35 (m, 1H), 2.21-2.11 (m, 1H), 1.98-1.87 (m, 1H), 1.83-1.72 (m, 1H).
Workup
- customevaporated
- dissolutionThe mixture was redissolved in EtOAc (40 mL)
- washwashed with 2N HCl (20 mL×3), brine, 5% NaHCO3 (20 mL×3), brine
- dry with materialdried with Na2SO4
- filtrationfiltered
- customevaporated
- customThe residue was purified by column chromatography on silica gel
- customto give a white solid (1.63 g, 56% for two steps)
Sources & evidence
- ORD record
- ord-37abab0d833d4ed6b72a3cd9ac56a8c5
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08202866B2
Reaction notes
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