Hydrochloric Acid → (S)-2-[4-(2,4-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

HRID 19086Notes

Reaction equation

C[O:2][C:3](=[O:24])[C@@H:4]([N:9]1[CH2:13][C:12]([O:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])=[CH:11][C:10]1=[O:23])[CH2:5][CH:6]([CH3:8])[CH3:7].O.[OH-].[Li+].Cl>O1CCCC1.O>[F:22][C:16]1[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][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]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of (S)-2-[4-(2,4-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (0.53 g, 1.58 mmol) in tetrahydrofuran (12 mL) and water (4 mL) was treated with lithium hydroxide monohydrate (80 mg, 1.89 mmol). The reaction was stirred at 25° C. for 4 h. At this time, the reaction was diluted with water (75 mL), acidified with a 2N aqueous hydrochloric acid solution and then extracted with 10% methanol/dichloromethane (3×50 mL). The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo to afford (S)-2-[4-(2,4-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.50 g, 97%) as a light yellow solid: HR-ES-MS m/z calculated for C16H17NO4F2 [M+Na]+ 348.1018, observed 348.1018; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.86 (d, J=6.4 Hz, 3H), 0.92 (d, J=6.4 Hz, 3H), 1.36-1.52 (m, 1H), 1.53-1.68 (m, 1H), 1.75-1.86 (m, 1H), 4.15 (d, J=18.4 Hz, 1H), 4.26 (d, J=18.4 Hz, 1H), 4.62 (dd, J=11.5, 4.2 Hz, 1H), 4.93 (s, 1H), 7.14-7.25 (m, 1H), 7.49-7.64 (m, 2H), 12.91 (br. s., 1H).

Workup

extractionextracted with 10% methanol/dichloromethane (3×50 mL)
dry with materialThe combined organics were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-32cb719e11e14f0bb3086488c333a1f2
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741327B2

Reaction notes

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