Citric Acid → HCID 66732569, compound

HRID 570613Notes

Reaction equation

HRID 570613 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH3:12])=[O:7])=[C:4]([F:15])[CH:3]=1.[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>[CH2:9]([NH:8][C:6]([C:5]1[CH:13]=[CH:14][C:2]([NH:16][C:17]([CH3:22])([CH3:21])[C:18]([OH:20])=[O:19])=[CH:3][C:4]=1[F:15])=[O:7])[CH2:10][CH2:11][CH3:12]

Participants

9

Reactant 5

HCID 311Citric AcidHCID 6119Aminoisobutyric acidHCID 11430Potassium CarbonateHCID 134002-AcetylcyclohexanoneHCID 24708843HCID 24708843, compound

Product 1

HCID 66732569HCID 66732569, compoundYield 94.3%

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, made in accordance with General Method 3, may be used to prepare compound 4 in accordance with General Method 1. 4-Bromo-N-butyl-2-fluorobenzamide (950 mg, 3.22 mmol), 2-aminoisobutyric acid (450 mg, 4.36 mmol), CuI (100 mg, 0.5 mmol), TEA (0.1 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 900 mg of 2-(4-(butylcarbamoyl)-3-fluorophenylamino)-2-methylpropanoic acid.

Workup

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

Sources & evidence

ORD record
ord-bc2a4e409e4245499351f7afd5a90664
Source dataset
uspto-grants-2015_05
Patent number
US09023869B2

Reaction notes

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