Lithium Hydroxide → 3-Iodo-1-(tetrahydro-pyran-2-yl)-1H-pyrazole-4-carboxylic acid

HRID 59719Notes

Reaction equation

HRID 59719 reaction equation
[I:1][C:2]1[C:6]([C:7]([O:9]CC)=[O:8])=[CH:5][N:4]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[N:3]=1.[Li+].[OH-]>C1COCC1.CO.O>[I:1][C:2]1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][N:4]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[N:3]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 58486565ethyl 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carboxylate

Product 1

HCID 904248953-Iodo-1-(tetrahydro-pyran-2-yl)-1H-pyrazole-4-carboxylic acidYield 96%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 3-iodo-1-(oxan-2-yl)-1H-pyrazole-4-carboxylate (85 g, 242.75 mmol, 1.00 equiv) in THF (300 mL) and methanol (300 mL) was added a solution of LiOH (17.5 g, 730.69 mmol, 3.01 equiv) in water (400 mL). The resulting solution was stirred at room temperature overnight and then concentrated under vacuum to remove the organic solvent. The resulting solution was diluted with 400 mL of H2O and then acidified to pH 6.0 with 1M hydrochloric acid. The mixture was extracted with 3×800 mL of dichloromethane. The combined organic layers was washed with 3×1000 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to give 75 g (96%) of 3-iodo-1-(oxan-2-yl)-1H-pyrazole-4-carboxylic acid as an off-white solid. LCMS (method D, ESI): RT=1.23 min, m/z=323.0 [M+H]+.

Workup

  1. concentrationconcentrated under vacuum
  2. customto remove the organic solvent
  3. additionThe resulting solution was diluted with 400 mL of H2O
  4. extractionThe mixture was extracted with 3×800 mL of dichloromethane
  5. washThe combined organic layers was washed with 3×1000 mL of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-dc4ce42c72d04365aa7c64b5c7587b9f
Source dataset
uspto-grants-2016_09
Patent number
US09440950B2

Reaction notes

Loading…