Lithium Hydroxide → HCID 66847779, compound

HRID 1631324Notes

Reaction equation

HRID 1631324 reaction equation
[Si]([O:8][C@H:9]1[CH2:13][N:12]([C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([O:25]CC)=[O:24])=[C:16]3[N:15]=2)[C@@H:11]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)[CH2:10]1)(C(C)(C)C)(C)C.[Li+].[OH-]>CCO>[F:34][C:30]1[CH:29]=[C:28]([C@H:11]2[CH2:10][C@@H:9]([OH:8])[CH2:13][N:12]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[C:16]3[N:15]=2)[CH:33]=[CH:32][CH:31]=1

Participants

4

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 66852075HCID 66852075, compound

Product 1

HCID 66847779HCID 66847779, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 5-((2R,4R)-4-(tert-butyldimethyl silyloxy)-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (205 mg, 0.422 mmol) was suspended in EtOH (2.0 mL) and 1M LiOH (0.845 ml, 0.845 mmol) was added. The mixture was heated at reflux for 4 hours and another portion of 1M LiOH (0.845 ml, 0.845 mmol) was added. The mixture was heated at reflux overnight, cooled to ambient temperature and concentrated. The residue was diluted in water and the mixture was treated with 2N HCl to achieve pH 1. The mixture was extracted with DCM and EtOAc and the combined extracts were dried with MgSO4, filtered and concentrated to afford 5-((2R,4R)-2-(3-fluorophenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (124 mg, 86%) as a light orange solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 4 hours
  3. temperatureThe mixture was heated
  4. temperatureat reflux overnight
  5. concentrationconcentrated
  6. additionThe residue was diluted in water
  7. additionthe mixture was treated with 2N HCl
  8. extractionThe mixture was extracted with DCM and EtOAc
  9. dry with materialthe combined extracts were dried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-2b6783540f6a4bdd97a22104c91e5f11
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

Loading…