Lithium hydroxide, monohydrate → (S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

HRID 19056노트

반응식

HRID 19056 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][CH:18]=[C:17]([Cl:21])[C:16]=2[F:22])=[CH:11][C:10]1=[O:23])[CH2:5][CH:6]([CH3:8])[CH3:7].O.[OH-].[Li+]>O1CCCC1.O>[Cl:21][C:17]1[C:16]([F:22])=[C:15]([CH:20]=[CH:19][CH:18]=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

5

반응물 2

HCID 168937Lithium hydroxide, monohydrateHCID 66893682(S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester

생성물 1

HCID 66895188(S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid수율 90%

시약·촉매·용매 2

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

반응 조건

온도
25 °C

실험 절차

A mixture of (S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (0.87 g, 2.46 mmol) in tetrahydrofuran (15 mL) and water (5 mL) was treated with lithium hydroxide monohydrate (0.12 g, 2.85 mmol). The reaction was stirred at 25° C. for 2.5 h. At this time, the reaction was diluted with water (75 mL) and extracted with diethyl ether (1×75 mL). The aqueous layer was acidified with a 2N aqueous hydrochloric acid solution and then extracted with ethyl acetate (3×50 mL). The combined organics were dried over magnesium sulfate, filtered, rinsed with ethyl acetate and concentrated in vacuo to afford (S)-2-[4-(3-chloro-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (0.75 g, 90%) as a light orange solid: HR-ES-MS m/z calculated for C16H17NO4FCl [M+H]+ 342.0903, observed 342.0904; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.87 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H), 1.35-1.56 (m, 1H), 1.56-1.70 (m, 1H), 1.72-1.86 (m, 1H), 4.19 (d, J=18.2 Hz, 1H), 4.29 (d, J=18.2 Hz, 1H), 4.63 (dd, J=11.5, 4.3 Hz, 1H), 5.05 (s, 1H), 7.33 (td, J=8.3, 1.4 Hz, 1H), 7.49-7.55 (m, 1H), 7.57 (ddd, J=8.3, 6.8, 1.4 Hz, 1H), 12.92 (br. s., 1H).

후처리

  1. extractionextracted with diethyl ether (1×75 mL)
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. washrinsed with ethyl acetate
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-6e8afce8241a43fea3d1f66d78bdb89e
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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