1-Aminocyclopropane-1-carboxylic acid → 1-(4-(Methylcarbamoyl)-3-fluorophenylamino)cyclopropanecarboxylic acid

HRID 570616Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][CH3:9])=[O:7])=[C:4]([F:12])[CH:3]=1.[NH2:13][C:14]1([C:17]([OH:19])=[O:18])[CH2:16][CH2:15]1.C([O-])([O-])=O.[K+].[K+].C(C1CCCCC1=O)(=O)C>CN(C=O)C.[Cu]I.C(N(CC)CC)C.O>[CH3:9][NH:8][C:6]([C:5]1[CH:10]=[CH:11][C:2]([NH:13][C:14]2([C:17]([OH:19])=[O:18])[CH2:16][CH2:15]2)=[CH:3][C:4]=1[F:12])=[O:7]

Participants

Conditions

Temperature: 100 °C

Procedure

To a stirred solution of 4-bromo-2-fluoro-N-methylbenzamide (6.4 g, 27.5 mmol), 1-aminocyclopropanecarboxylic acid (4.29 g, 42.4 mmol), CuI (1.047 g, 5.5 mmol), K2CO3 (9.50 g, 68.0 mmol), in DMF (64 mL) was added H2O (6.4 mL), triethylamine (0.164 mL, 1.1 mmol) followed by 2-acetyl cyclohexanone (0.717 g, 5.10 mmol). The reaction mixture was stirred at 100° C. overnight. The reaction was monitored by TLC and LCMS. H2O was added, and the aqueous layer was washed with ethyl acetate. The aqueous layer was acidified with 1M citric acid solution (pH˜4) and extracted with ethyl acetate. The organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and crystallized with DCM to afford 3.01 g of the title compound as an off-white solid.

Workup

washthe aqueous layer was washed with ethyl acetate
extractionextracted with ethyl acetate
dry with materialThe organic extracts were dried over anhydrous Na2SO4
concentrationconcentrated under reduced pressure
customcrystallized with DCM

Sources & evidence

ORD record: ord-14a037a9fdc54852a630c04ceb9c4ab6
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023869B2

Reaction notes

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