Aminoisobutyric acid → 2-((4-Carbamoyl-3-fluorophenyl)amino)-2-methylpropanoic acid

HRID 570766Notes

Reaction equation

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

Participants

Conditions

Temperature: 97.5 °C

Procedure

4-Bromo-2-fluorobenzamide (0.5 g, 2.29 mmol), 2 aminoisobutyric acid (0.354 g, 3.54 mmol), CuI (87 mg, 0.458 mmol), and K2CO3 (0.790 g, 5.72 mmol) were mixed in DMF (5 mL). H2O (0.5 mL) and TEA (11 mg, 0.1 mmol) were added followed by 2-acetyl cyclohexanone (60 mg, 0.428 mmol). The reaction mixture was heated to 95-100° C. for 48 h. The reaction mixture was diluted with H2O (20 mL) and the aqueous layer was washed with ethyl acetate (20 mL). The aqueous layer was acidified with 1M citric acid to pH 4 and the product was extracted with ethyl acetate (20 mL×3). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the product. 1H NMR (DMSO, Freebase): δ (ppm) 7.55-7.45 (t, 1H), 7.20 (bs, 1H), 7.05 (bs, 1H), 6.80 (bs, 1H), 6.35-6.30 (d, 1H), 6.18-6.10 (d, 1H), 1.42 (s, 6H).

Workup

washthe aqueous layer was washed with ethyl acetate (20 mL)
extractionthe product was extracted with ethyl acetate (20 mL×3)
dry with materialThe combined organic layer was dried over anhydrous Na2SO4
concentrationconcentrated under reduced pressure
customto obtain the product

Sources & evidence

ORD record: ord-1f2512f0752140e1bac7469b8b9e22f1
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023879B2

Reaction notes

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