Citric Acid → HCID 66732558, compound

HRID 2274378Notes

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-970cb89da5c94c8c9822f954cfe5a20f
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09126962B2

Reaction notes

Loading…