Citric Acid → HCID 66732558, compound

HRID 570615Notes

Reaction equation

Br[C:2]1[CH:13]=[CH:12][C:5]([C:6]([NH:8][CH2:9][CH2:10][CH3:11])=[O:7])=[C:4]([F:14])[CH:3]=1.[NH2:15][C:16]([CH3:21])([CH3:20])[C:17]([OH:19])=[O:18].C([O-])([O-])=O.[K+].[K+].C(C1CCCCC1=O)(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.[Cu]I.O>[CH2:9]([NH:8][C:6]([C:5]1[CH:12]=[CH:13][C:2]([NH:15][C:16]([CH3:21])([CH3:20])[C:17]([OH:19])=[O:18])=[CH:3][C:4]=1[F:14])=[O:7])[CH2:10][CH3:11]

Participants

Conditions

Temperature: 100 °C

Procedure

The title compound, made in accordance with General Method 3, may be used to prepare compound 5 in accordance with General Method 1. 4-Bromo-2-fluoro-N-propylbenzamide (620 mg, 2.39 mmol), 2-aminoisobutyric acid (422 mg, 4.09 mmol), CuI (100 mg, 0.6 mmol), TEA (catalytic amount) and K2CO3 (1.13 g, 8.1 mmol) were dissolved in DMF (8 mL) and water (2 mL) stirred at RT for 5 min. 2-Acetylcyclohexanone (0.13 g, 0.3 mmol) was added and the reaction mixture was heated at 100° C. for 18 h. The reaction mixture was acidified with 1 M citric acid (pH 4) and extracted with ethyl acetate (100 mL, 2 times). The combined organic layer was dried over Na2SO4 and concentrated to obtain 1.0 g of 2-(4-(propylcarbamoyl)-3-fluorophenylamino)-2-methylpropanoic acid.

Workup

extractionextracted with ethyl acetate (100 mL, 2 times)
dry with materialThe combined organic layer was dried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-766f4f1440564be48f8a312e91a51258
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023869B2

Reaction notes

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