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

HRID 19086노트

반응식

HRID 19086 반응식
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

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 66894883(S)-2-[4-(2,4-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester

생성물 1

HCID 66894852(S)-2-[4-(2,4-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid수율 97.3%

시약·촉매·용매 2

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

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온도
25 °C

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-32cb719e11e14f0bb3086488c333a1f2
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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