Lithium hydroxide, monohydrate → ((1S)-5-{3-[4-(4-ethyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 603422Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 603422
[CH2:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:33]=[CH:32][C:11]([O:12][CH2:13][CH2:14][CH2:15][O:16][C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[C@H:22]([CH2:26][C:27]([O:29]CC)=[O:28])[CH2:21][CH2:20]4)=[C:10]([CH2:34][CH2:35][CH3:36])[CH:9]=2)[S:6][CH:7]=1)[CH3:2].O[Li].O>C1COCC1.O.CO>[CH2:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:33]=[CH:32][C:11]([O:12][CH2:13][CH2:14][CH2:15][O:16][C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[C@H:22]([CH2:26][C:27]([OH:29])=[O:28])[CH2:21][CH2:20]4)=[C:10]([CH2:34][CH2:35][CH3:36])[CH:9]=2)[S:6][CH:7]=1)[CH3:2]

Komponenten

6

Edukt 2

HCID 168937Lithium hydroxide, monohydrateHCID 16110452ethyl ((1S)-5-{3-[4-(4-ethyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Produkt 1

HCID 16110486((1S)-5-{3-[4-(4-ethyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acidAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of ethyl ((1S)-5-{3-[4-(4-ethyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (60 mg 0.12 mmol) (Example 147) in THF (3.0 mL) was added a solution of LiOH.H2O (20 mg, 0.48 mmol) in water (1.0 mL) and MeOH (1.0 mL), and the mixture was stirred for 12 h at rt. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water and extracted with Et2O (3×). The aqueous phase was brought to pH 3 using HCl (1N aqueous solution), and then the aqueous layer was extracted with EtOAc. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure to give 36 mg (63%) of the title compound as a white solid. 1H NMR (300 MHz, CD3OD): δ0.96 (t, 3H), 1.34 (t, 3H), 1.59-1.71 (m, 2H), 1.73-1.81 (m, 1H), 2.25-2.38 (m, 2H), 2.39-2.47 (m, 2H), 2.62-2.98 (m, 7H), 3.44-3.57 (m, 1H), 4.20 (t, 2H), 4.26 (t, 2H), 6.75 (d, 1H), 6.84 (s, 1H), 7.02 (d, 1H), 7.07 (s, 1H), 7.14 (d, 1H), 7.71 (s, 1H), 7.78 (d, 1H); LC-MS: RT=4.04 min, (M+H)+ 480.2.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with water
  3. extractionextracted with Et2O (3×)
  4. extractionthe aqueous layer was extracted with EtOAc
  5. dry with materialThe organic phase was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-6658b6c32168487a93d978eb96f35dc3
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07906653B2

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