Citric Acid → HCID 66731962, compound

HRID 2370353Notes

Reaction equation

HRID 2370353 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

9

Reactant 5

HCID 311Citric AcidHCID 6119Aminoisobutyric acidHCID 11430Potassium CarbonateHCID 134002-AcetylcyclohexanoneHCID 223362524-Bromo-N-tert-butyl-2-fluorobenzamide

Product 1

HCID 66731962HCID 66731962, compoundYield 108.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

The title compound was prepared according to General Method 7. 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

  1. customThe title compound was prepared
  2. extractionextracted with ethyl acetate (50 mL, 2 times)
  3. dry with materialThe combined organic layer was dried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-eccd69e3ca9f4232aba44f6cc84e6489
Source dataset
uspto-grants-2014_04
Patent number
US08710086B2

Reaction notes

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