Citric Acid → HCID 66731962, compound

HRID 570614Notes

Reaction equation

[C:1]([NH:5][C:6](=[O:15])[C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][C:8]=1[F:14])([CH3:4])([CH3:3])[CH3:2].[NH2:16][C:17]([CH3:22])([CH3:21])[C:18]([OH:20])=[O:19].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>[C:1]([NH:5][C:6]([C:7]1[CH:12]=[CH:11][C:10]([NH:16][C:17]([CH3:22])([CH3:21])[C:18]([OH:20])=[O:19])=[CH:9][C:8]=1[F:14])=[O:15])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

The title compound, made in accordance with General Method 3, may be used to prepare compound 3 in accordance with General Method 1. N-tert-Butyl-4-bromo-2-fluorobenzamide (850 mg, 3.1 mmol), 2-aminoisobutyric acid (450 mg, 4.36 mmol), CuI (100 mg, 0.5 mmol), TEA (0.2 mL) and K2CO3 (1.0 g, 7.2 mmol) were charged in DMF (8 mL) and water (2 mL) and stirred at RT for 5 min. 2-Acetylcyclohexanone (100 mg, 0.7 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 (50 mL, 2 times). The combined organic layer was dried over Na2SO4 and concentrated to obtain 1.0 g of 2-(4-(tert-butylcarbamoyl)-3-fluorophenylamino)-2-methylpropanoic acid.

Workup

extractionextracted with ethyl acetate (50 mL, 2 times)
dry with materialThe combined organic layer was dried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-0cfd027c2a1f49dbb5b991dae66d4545
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09023869B2

Reaction notes

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