Lithium hydroxide, monohydrate → ((1S)-5-{3-[(3-methyl-1-benzofuran-6-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 2235875Notes

Reaction equation

HRID 2235875 reaction equation
C([O:3][C:4](=[O:30])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:29]=[CH:28][C:23]4[C:24]([CH3:27])=[CH:25][O:26][C:22]=4[CH:21]=3)=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)C.O[Li].O>C1COCC1.O>[CH3:27][C:24]1[C:23]2[CH:28]=[CH:29][C:20]([O:19][CH2:18][CH2:17][CH2:16][O:15][C:11]3[CH:10]=[C:9]4[C:14](=[CH:13][CH:12]=3)[C@H:6]([CH2:5][C:4]([OH:30])=[O:3])[CH2:7][CH2:8]4)=[CH:21][C:22]=2[O:26][CH:25]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59300536ethyl ((1S)-5-{3-[(3-methyl-1-benzofuran-6-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 24776386((1S)-5-{3-[(3-methyl-1-benzofuran-6-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acidYield 22%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of ethyl((1S)-5-{3-[(3-methyl-1-benzofuran-6-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (119 mg, 0.29 mmol) (Example 64) in THF (4.2 mL) was added a solution of LiOH.H2O (15 mg, 0.35 mmol) in water (1.4 mL). The mixture was stirred for 4 h at 45° C. and then 12 h at rt. The reaction mixture was concentrated under reduced pressure, water was added, and the aqueous phase was washed with a small volume of Et2O. The pH was adjusted to below 3 with HCl (1 N aqueous solution), and the aqueous phase was extracted with excess EtOAc. The combined EtOAc extracts were dried, filtered, and concentrated under reduced pressure to give 24 mg (22%) of the title compound as a solid. 1H NMR (300 MHz, CDCl3): δ 7.44-7.22 (m, 2H), 7.08 (d, 1H), 6.98 (s, 1H), 6.89 (d, 1H), 6.80 (s, 1H), 6.72 (d, 1H), 4.32-4.04 (m, 4H), 3.63-3.44 (m, 1H), 2.98-2.76 (m, 3H), 2.58-2.37 (m, 2H), 2.37-2.14 (m, 5H), 1.88-1.70 (m, 1H); LC-MS: RT=3.53 min, (M+H)+ 381.1.

Workup

  1. custom12 h
  2. customat rt
  3. concentrationThe reaction mixture was concentrated under reduced pressure, water
  4. additionwas added
  5. washthe aqueous phase was washed with a small volume of Et2O
  6. extractionthe aqueous phase was extracted with excess EtOAc
  7. dry with materialThe combined EtOAc extracts were dried
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-88836180ad8949c78427f3745ddeaca7
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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