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

HRID 526765Notes

Reaction equation

HRID 526765 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-].Cl>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 3

HCID 313Hydrochloric AcidHCID 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 76.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of ethyl 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carboxylate (5 g, 14.2 mmol) in (1:1) THF/MeOH (32 mL) was added a solution of LiOH (1.8 g, 4.28 mmol) in water (16 mL). The reaction was stirred at rt for 4 h then evaporated under vacuum and the residue was treated with water (25 mL) and washed with ethyl acetate (30 mL×2). The aqueous layer was isolated acidified to ˜pH5 with 2N HCl and extracted with DCM (30 mL×3). The combined extracts were washed with brine (30 mL), dried and concentrated to afford 3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-4-carboxylic acid (3.5 g, yield: 76%). LCMS (method B): RT=2.18 min, m/z=321.0 [M−H]−.

Workup

  1. customthen evaporated under vacuum
  2. additionthe residue was treated with water (25 mL)
  3. washwashed with ethyl acetate (30 mL×2)
  4. customThe aqueous layer was isolated
  5. extractionextracted with DCM (30 mL×3)
  6. washThe combined extracts were washed with brine (30 mL)
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6031bf2a06964d8f9cebeb2a640d7f79
Source dataset
uspto-grants-2016_05
Patent number
US09346761B2

Reaction notes

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