Diethyl Ether → (S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid

HRID 18981노트

반응식

HRID 18981 반응식
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]=1

참가 물질

6

반응물 3

HCID 3283Diethyl EtherHCID 3939Lithium HydroxideHCID 66895169(S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester

생성물 1

HCID 66894519(S)-2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid수율 82.4%

시약·촉매·용매 2

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

반응 조건

온도
25 °C

실험 절차

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.

후처리

  1. additionAfter addition
  2. customthe layers separated
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. washThe combined ethyl acetate fractions were washed with a saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-9d567acc530d47c99f801dbaf02021b5
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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