Diethyl Ether → (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid
Reaction equation
C[O:2][C:3](=[O:24])[C@@H:4]([N:9]1[CH2:13][C:12]([O:14][C:15]2[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=2[F:22])=[CH:11][C:10]1=[O:23])[CH2:5][CH:6]([CH3:8])[CH3:7].[OH-].[Li+].C(OCC)C>O1CCCC1.O>[F:22][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]([F:21])[C:15]=1[O:14][C:12]1[CH2:13][N:9]([C@@H:4]([CH2:5][CH:6]([CH3:8])[CH3:7])[C:3]([OH:24])=[O:2])[C:10](=[O:23])[CH:11]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 25 °C
Procedure
To a stirred mixture of (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (900 mg, 2.65 mmol) in tetrahydrofuran (10 mL) and water (3 mL) was added lithium hydroxide (135 mg, 3.19 mmol). After addition was complete the mixture was stirred at 25° C. for 2 h. The reaction mixture was poured into water and diethyl ether and the layers separated. The aqueous layer was made acidic with 2N aqueous hydrochloric acid and extracted with ethyl acetate (3×30 mL). The combined ethyl acetate fractions were washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to afford (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (710 mg, 82%) as a yellow solid: LR-ES-MS m/z calculated for C16H17F2NO4 [M]+ 325, observed [M+H]+ 326.
Workup
- additionAfter addition
- customthe layers separated
- extractionextracted with ethyl acetate (3×30 mL)
- washThe combined ethyl acetate fractions were washed with a saturated sodium chloride solution
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-9d567acc530d47c99f801dbaf02021b5
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07741327B2
Reaction notes
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