Water → HCID 90114262, compound
Reaction equation
[NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[F:14])[CH2:3][C:4]([OH:6])=[O:5].[C:15]1(=O)[O:20][C:18](=[O:19])[C:17]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]12.O>CN(C=O)C>[F:14][C:8]1[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=1[CH:2]([N:1]1[C:18](=[O:19])[C:17]2[C:16](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]1=[O:20])[CH2:3][C:4]([OH:6])=[O:5]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 135 °C
Procedure
5.0 g of rac-3-amino-3-(2,4-difluorophenyl)propanoic acid (24.85 mmol) and 3.68 g of phthalic anhydride (24.85 mmol) were dissolved in 20 ml of DMF and the mixture was heated at reflux at 135° C. overnight. The reaction solution was added to about 160 ml of water and extracted twice with ethyl acetate. The combined organic phases were washed with water, dried over sodium sulphate, filtered and concentrated. The crude product was purified by silica gel chromatography (mobile phase: dichloromethane/methanol 80:1, isocratic) and then by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). This gave 3.43 g of the title compound (27% of theory).
Workup
- temperaturethe mixture was heated
- extractionextracted twice with ethyl acetate
- washThe combined organic phases were washed with water
- dry with materialdried over sodium sulphate
- filtrationfiltered
- concentrationconcentrated
- customThe crude product was purified by silica gel chromatography (mobile phase: dichloromethane/methanol 80:1, isocratic)
- additionby preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
Sources & evidence
- ORD record
- ord-eb81a8025b594241a191b0ee7ddf3bfa
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09126998B2
Reaction notes
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