Lithium hydroxide, monohydrate → [(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]acetic acid

HRID 1876311Notes

Reaction equation

HRID 1876311 reaction equation
C[O:2][C:3](=[O:26])[CH2:4][C@@H:5]1[CH2:9][S:8][C:7]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([Cl:19])=[CH:14][C:13]=3[NH:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[N:6]1.O.[OH-].[Li+]>O1CCCC1.CO.O>[Cl:19][C:15]1[CH:16]=[C:17]2[C:12](=[C:13]([NH:20][CH:21]3[CH2:22][CH2:23][CH2:24][CH2:25]3)[CH:14]=1)[NH:11][C:10]([C:7]1[S:8][CH2:9][C@@H:5]([CH2:4][C:3]([OH:26])=[O:2])[N:6]=1)=[CH:18]2

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 25196144[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]acetic acid methyl ester

Product 1

HCID 25196145[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]acetic acidYield 905.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The compound (1.5 g, 3.83 mmol) prepared in Example 26 was dissolved in tetrahydrofuran (100 ml) and methanol (50 ml). Lithium hydroxide monohydrate (640 mg, 15.3 mmol) was dissolved in water (50 ml) and added to the reaction solution, which was then stirred for 4 h at room temperature. After completion of the reaction, the reaction solution was distilled under reduced pressure to remove tetrahydrofuran and methanol. 1N hydrochloric acid solution was added to the residue, and the mixture was extracted with ethyl acetate, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The filtrate was distilled under reduced pressure and separated by column chromatography to give the title compound (13.1 g, Yield 92%).

Workup

  1. additionadded to the reaction solution, which
  2. customAfter completion of the reaction
  3. distillationthe reaction solution was distilled under reduced pressure
  4. customto remove tetrahydrofuran and methanol
  5. addition1N hydrochloric acid solution was added to the residue
  6. extractionthe mixture was extracted with ethyl acetate
  7. washwashed with saturated sodium chloride solution
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. distillationThe filtrate was distilled under reduced pressure
  11. customseparated by column chromatography

Sources & evidence

ORD record
ord-b18d7095108d4e77b1d4f2b8d535ab43
Source dataset
uspto-grants-2012_11
Patent number
US08309586B2

Reaction notes

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