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

HRID 603394Notes

Reaction equation

HRID 603394 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][CH2:12][CH2:13][CH2:14][O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[C@H:21]([CH2:25][C:26]([O:28]CC)=[O:27])[CH2:20][CH2:19]4)=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.O[Li].O>C1COCC1.O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][CH2:12][CH2:13][CH2:14][O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[C@H:21]([CH2:25][C:26]([OH:28])=[O:27])[CH2:20][CH2:19]4)=[CH:8][CH:9]=2)[CH:4]=[CH:3]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59300453ethyl((1S)-5-{3-[(1-methyl-1H-indol-5-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 24776388((1S)-5-{3-[(1-methyl-1H-indol-5-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acidYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl ((1S)-5-{3-[(1-methyl-1H-indol-5-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (51 mg, 0.13 mmol) (Example 48) in THF (1.8 mL) was added LiOH.H2O (6 mg, 0.15 mmol) in water (0.6 mL). The mixture was stirred for 12 h at rt, then the reaction mixture was concentrated under reduced pressure and the residue suspended in a small volume of water. The pH was adjusted to below 3 with HCl (1 N aqueous solution), and the aqueous layer was extracted with EtOAc. The organic layer was dried, filtered, and concentrated under reduced pressure to give 44 mg (93%) of the title compound as a solid. 1H NMR (400 MHz, CDCl3): δ 7.10 (d, 1H), 7.05-6.96 (m, 2H), 6.93 (d, 1H), 6.81 (dd, 1H), 6.72 (s, 1H), 6.65 (dd, 1H), 6.32 (d, 1H), 4.18-4.00 (m, 4H), 3.69 (s, 3H), 3.52-3.40 (m, 1H), 2.92-2.65 (m, 3H), 2.42-2.24 (m, 2H), 2.22-2.10 (m, 2H), 1.78-1.62 (m, 1H); LC-MS RT=3.45 min, (M+H)+ 380.1.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. extractionthe aqueous layer was extracted with EtOAc
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fa49dace0a9540fdaa5a3d66c01b4ae0
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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