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Lithium Hydroxide → ((1S)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 2098967
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HRID 2098967 반응식
[CH2:1]([O:5][C:6]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:22]=[C:21]3[C:17]([CH2:18][CH2:19][C@H:20]3[CH2:23][C:24]([O:26]C)=[O:25])=[CH:16][CH:15]=2)[CH:9]=[CH:8][C:7]=1[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=1[F:36])[CH2:2][CH2:3][CH3:4].[OH-].[Li+]>C1COCC1.CO>[CH2:1]([O:5][C:6]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:22]=[C:21]3[C:17]([CH2:18][CH2:19][C@@H:20]3[CH2:23][C:24]([OH:26])=[O:25])=[CH:16][CH:15]=2)[CH:9]=[CH:8][C:7]=1[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=1[F:36])[CH2:2][CH2:3][CH3:4].[CH2:1]([O:5][C:6]1[CH:11]=[C:10]([CH2:12][O:13][C:14]2[CH:22]=[C:21]3[C:17]([CH2:18][CH2:19][C@H:20]3[CH2:23][C:24]([OH:26])=[O:25])=[CH:16][CH:15]=2)[CH:9]=[CH:8][C:7]=1[C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=1[F:36])[CH2:2][CH2:3][CH3:4]
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5

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HCID 3939Lithium HydroxideHCID 59590932methyl ((1S)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetate

생성물 2

HCID 44223268((1R)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acidHCID 44223269((1S)-6-(((2-(butyloxy)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acid
수율 84.4%

시약·촉매·용매 1

HCID 21899815MeOH tetrahydrofuran용매

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온도
23 °C

실험 절차

To a solution of 17.1 (0.024 g, 0.0485 mmol) in THF/MeOH (2/1) (1.5 mL) was added lithium hydroxide (0.50 mL, 0.50 mmol). The resulting mixture was stirred overnight at 23° C., quenched with excess 1N HCl, and extracted with EtOAc. The combined organic layers were dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel chromatography (0 to 40% EtOAc/hexanes) to afford ((1R)-6-(((2-(butyloxy)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acid or ((1S)-6-(((2-(butyloxy)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-4-yl)methyl)oxy)-2,3-dihydro-1H-inden-1-yl)acetic acid 17 (0.0098 g, 42% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.26-7.31 (1H, m), 7.15 (1H, d, J=7.8 Hz), 7.00-7.09 (3H, m), 6.81-6.90 (4H, m), 5.07 (2H, s), 4.00 (2H, t, J=6.5 Hz), 3.80 (3H, s), 3.59 (1H, m), 2.78-2.94 (3H, m), 2.55-2.40 (2H, m), 1.86-1.76 (1H, m), 1.64-1.71 (2H, m), 1.33-1.43 (2H, m), 0.89 (3H, t, J=7.4 Hz).

후처리

  1. customquenched with excess 1N HCl
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (0 to 40% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-62b6f9598fb746cea25a7429c1daa031
출처 데이터셋
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08450522B2

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