Reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[F:11].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.C(N(CC)C(C)C)(C)C.[F:50][C:51]1[CH:62]=[CH:61][C:54]([O:55][C:56]([CH3:60])([CH3:59])[CH2:57][NH2:58])=[CH:53][CH:52]=1>>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:58][CH2:57][C:56]([O:55][C:54]2[CH:53]=[CH:52][C:51]([F:50])=[CH:62][CH:61]=2)([CH3:60])[CH3:59])=[O:8])=[CH:4][C:3]=1[F:11]Participants
6
Reactant 5
Product 1
Procedure
To a mixture of 4-amino-3-fluorobenzoic acid (200.0 mg, 1.289 mmol) and HBTU (490 mg, 1.3 mmol) in DMF (2 mL, 20 mmol) at 0° C. were added N,N-diisopropylethylamine (0.67 mL, 3.9 mmol) and 2-(4-fluorophenoxy)-2-methylpropan-1-amine (Preparation 91, 280 mg, 1.5 mmol). The reaction mixture was slowly warmed to ambient temperature. The reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic layers were washed successively with water, aqueous lithium chloride, and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform).
Workup
- customThe reaction mixture was quenched with an equal volume of saturated aqueous sodium bicarbonate
- extractionextracted with ethyl acetate (3×)
- washThe combined organic layers were washed successively with water, aqueous lithium chloride, and brine
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified on the Isco (120 g cartridge, chloroform to 12% MeOH in chloroform)
Sources & evidence
- ORD record
- ord-a21d075e470f4516997390ef108200d2
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08357711B2
Linked notes
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