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

HRID 603389Notes

Reaction equation

HRID 603389 reaction equation
[CH2:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:32]=[CH:31][C:11]([O: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)=[C:10]([CH2:33][CH2:34][CH3:35])[CH:9]=2)[S:6][CH:7]=1)[CH3:2].O[Li].O>C1COCC1.O>[CH2:1]([C:3]1[N:4]=[C:5]([C:8]2[CH:32]=[CH:31][C:11]([O: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)=[C:10]([CH2:33][CH2:34][CH3:35])[CH:9]=2)[S:6][CH:7]=1)[CH3:2]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59300542ethyl ((1S)-5-{2-[4-(4-ethyl-1,3-thiazol-2-yl)-2-propylphenoxy]-ethoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 59300431((1S)-5-{2-[4-(4-ethyl-1,3-thiazol-2-yl)-2-propylphenoxy]ethoxy}-2,3-dihydro-1H-inden-1-yl)acetic acidYield 13%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl ((1S)-5-{2-[4-(4-ethyl-1,3-thiazol-2-yl)-2-propylphenoxy]ethoxy}-2,3-dihydro-1H-inden-1-yl)acetate (18 mg, 0.04 mmol) (Example 35) in THF (1.2 mL), was added a solution of LiOH.H2O (5 mg, 0.11 mmol) in H2O (0.4 mL). The mixture was stirred for 12 h at rt. The reaction mixture was concentrated under reduced pressure, and the residue was suspended in a small volume of water. Then, HCl (1 N aqueous solution) was added until the solution was below pH 3. The aqueous layer was extracted with excess EtOAc, and the organic layer was dried, filtered and then concentrated to give the crude product. The residue was purified by HPLC (C18 reverse phase column, using 0-80% CH3CN in water) to give 2.2 mg (13%) of the title compound as a white solid. LC-MS: RT3.78 min; (M+H)+:466.4.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionThen, HCl (1 N aqueous solution) was added until the solution
  3. extractionThe aqueous layer was extracted with excess EtOAc
  4. customthe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product
  8. customThe residue was purified by HPLC (C18 reverse phase column

Sources & evidence

ORD record
ord-d92aa9d492b740f2a65043f9033990f9
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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