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Lithium Hydroxide → ((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 603414
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HRID 603414 반응식
[CH3:1][O:2][C:3]1[CH:28]=[C:27]([C:29]2[CH:33]=[CH:32][S:31][CH:30]=2)[CH:26]=[CH:25][C:4]=1[O:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[C@H:15]([CH2:19][C:20]([O:22]CC)=[O:21])[CH2:14][CH2:13]2.[Li+].[OH-]>CCO.C1COCC1.O>[CH3:1][O:2][C:3]1[CH:28]=[C:27]([C:29]2[CH:33]=[CH:32][S:31][CH:30]=2)[CH:26]=[CH:25][C:4]=1[O:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[C@H:15]([CH2:19][C:20]([OH:22])=[O:21])[CH2:14][CH2:13]2
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HCID 3939Lithium HydroxideHCID 59300464ethyl ((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

생성물 1

HCID 59300514((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acid수율 76%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매
HCID 8028
Tetrahydrofuran
용매

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온도
50 °C

실험 절차

The ester prepared in Example 98 (83 mg 0.18 mmol) was dissolved in a mixture of EtOH (3 mL), THF (3 mL), and water (1 mL), LiOH (42.6 mg, 1.78 mmol) was added and the reaction mixture was heated at 50° C. for 3 h. The reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with EtOAc. The combined organic phases were dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by preparative HPLC (CH3CN, 0.01% TFA/Water, 0.01% TFA (v/v)=2:3 to 100% CH3CN, 0.01% TFA) to give 60 mg (73%) of the title compound as a white solid. 1H NMR (400 MHz, acetone-d6): δ 7.62-7.61 (m, 1H), 7.52-7.47 (m, 2H), 7.29 (d, 1H), 7.23-7.20 (m, 1H), 7.14 (d, 1H), 7.01 (d, 1H), 6.33-6.32 (m, 1H), 6.77-6.74 (m, 1H), 4.23-4.18 (m, 4H), 3.89 (s, 3H), 3.48-3.45 (m, 1H), 3.22-2.71 (b, 1H), 2.93-2.71 (m, 3H), 2.42-2.32 (m, 2H), 2.28-2.22 (q, 2H), 1.76-1.70 (m, 1H). LC-MS: RT=5.28 min, (M−H) 437.3.

후처리

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additiondiluted with water
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by preparative HPLC (CH3CN, 0.01% TFA/Water, 0.01% TFA (v/v)=2:3 to 100% CH3CN, 0.01% TFA)

출처 및 근거

ORD 기록
ord-c7e205ac620a427b881a46b8ec5de9f8
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07906653B2

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