Citric Acid → 4-Amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl cyclopentenecarboxylate

HRID 17506Notes

Reaction equation

[NH2:1][C:2]1[C:9]([OH:10])=[C:8]([F:11])[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:6]([CH3:18])[C:3]=1[C:4]#[N:5].C(N(CC)CC)C.[C:26]1([C:31](Cl)=[O:32])[CH2:30][CH2:29][CH2:28][CH:27]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(#N)C>[C:26]1([C:31]([O:10][C:9]2[C:8]([F:11])=[C:7]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:6]([CH3:18])=[C:3]([C:4]#[N:5])[C:2]=2[NH2:1])=[O:32])[CH2:30][CH2:29][CH2:28][CH:27]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Under nitrogen atmosphere, 2-amino-5-phenyl-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-41) (200 mg, 0.83 mmol) was dissolved in acetonitrile (10 ml), and cooled to 0° C. Triethylamine (195 μl, 1.4 mmol) and cyclopentenecarbonyl chloride (162 mg, 1.24 mmol) were dropwise added to the solution, followed by stirring at room temperature for 1 hour. 10% citric acid was added to the reaction liquid, and the solvent was evaporated away under reduced pressure. Ethyl acetate was added to the resulting residue, followed by washing with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated away under reduced pressure. The resulting residue was subjected to preparative silica gel column chromatography, and the eluate with ethyl acetate/hexane (1:3, v/v) gave the entitled compound (180 mg, 77%) as a white solid.

Workup

customthe solvent was evaporated away under reduced pressure
additionEthyl acetate was added to the resulting residue
washby washing with saturated brine
dry with materialThe organic layer was dried over anhydrous magnesium sulfate
customthe solvent was evaporated away under reduced pressure

Sources & evidence

ORD record: ord-aff968b72d364d3fad2fd0fb7189e419
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07737166B2

Reaction notes

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