t-Butyl bromide → 2-Isopropyl-3-(1-hydroxy-2,2-dimethylpropyl)pyrazolo[1,5-a]pyridine

HRID 483086Notes

Reaction equation

HRID 483086 reaction equation
[Mg].[C:2](Br)([CH3:5])([CH3:4])[CH3:3].[CH:7]([C:10]1[C:18]([CH:19]=[O:20])=[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][N:12]2[N:11]=1)([CH3:9])[CH3:8].[Cl-].[NH4+]>CCOCC.C1C=CC=CC=1>[CH:7]([C:10]1[C:18]([CH:19]([OH:20])[C:2]([CH3:5])([CH3:4])[CH3:3])=[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][N:12]2[N:11]=1)([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 10485t-Butyl bromideHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 143032672-Isopropylpyrazolo[1,5-a]pyridine-3-carbaldehyde

Product 1

HCID 133917102-Isopropyl-3-(1-hydroxy-2,2-dimethylpropyl)pyrazolo[1,5-a]pyridineYield 52%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 3283Diethyl EtherSolvent2×

Procedure

To a suspension of 1.6 g of magnesium in 10 ml of dry ether was added a solution of 9.3 g of tert. butylbromide in 15 ml of dry ether under stirring. After the addition was completed, the stirring was continued for an hour at room temperature. To the Grignard reagent were added 2.5 g of 2-isopropyl-3-formylpyrazolo[1,5-a]pyridine in 5 ml of dry benzene under stirring. The mixture was stirred for an hour at room temperature and 11 hours at reflux temperature. The reaction mixture was treated with 100 ml of aqueous 20% ammonium chloride solution and extracted with ether. The ether layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was subjected to silica gel column chromatography, eluted with dichloromethane, to give 1.7 g (52%) of pale yellow crystals, mp 95° C.

Workup

  1. additionAfter the addition
  2. waitthe stirring was continued for an hour at room temperature
  3. stirringunder stirring
  4. stirringThe mixture was stirred for an hour at room temperature and 11 hours
  5. temperatureat reflux temperature
  6. extractionextracted with ether
  7. washThe ether layer was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. washeluted with dichloromethane

Sources & evidence

ORD record
ord-161c696e45d14edca61a910d1821d2e3
Source dataset
uspto-grants-1986_03
Patent number
US04578392

Reaction notes

Loading…