Ammonium Chloride → (5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)(4-chloro-2-methylphenyl)methanol

HRID 1748823Notes

Reaction equation

HRID 1748823 reaction equation
[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:3]=1[CH:14]=[O:15].[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([Mg]Br)=[C:19]([CH3:25])[CH:18]=1.[NH4+].[Cl-]>C1COCC1>[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[C:3]=1[CH:14]([C:20]1[CH:21]=[CH:22][C:17]([Cl:16])=[CH:18][C:19]=1[CH3:25])[OH:15]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 867241455-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazole-4-carbaldehydeHCID 178426105HCID 178426105, compound

Product 1

HCID 86724146(5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)(4-chloro-2-methylphenyl)methanolYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazole-4-carbaldehyde (16.38 g, 73.9 mmol) in THF (350 mL) was cooled to about −40 to −50° C. then 0.5 M (4-chloro-2-methylphenyl)magnesium bromide in THF (163 mL, 81 mmol) was added dropwise over about 15 min. The mixture was allowed to warm to rt then cooled in an ice bath. Saturated aqueous NH4Cl (400 mL) was added then the mixture was extracted with EtOAc (2×300 mL). The organic layer was washed by brine (400 mL), dried over Na2SO4, filtered and concentrated in vacuo to give (5-chloro-1-methyl-3-(pyridin-2-yl)-1H-pyrazol-4-yl)(4-chloro-2-methylphenyl)methanol (25.7 g, 100%): LC-MS (Table 1, Method g) Rt=2.49 min, m/z 348/350 (M+H)+; 1H-NMR (DMSO, Bruker 400 MHz) δ 8.56 (d, J=5.0 Hz, 1H), 8.03 (d, J=8.1 Hz, 1H), 7.96-7.90 (m, 1H), 7.40-7.36 (m, 1H), 7.22-7.16 (m, 3H), 7.09-7.05 (m, 1H), 6.23 (d, J=7.8 Hz, 1H), 3.87 (s, 3H), 2.26 (s, 3H).

Workup

  1. temperaturethen cooled in an ice bath
  2. extractionthe mixture was extracted with EtOAc (2×300 mL)
  3. washThe organic layer was washed by brine (400 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cbb4890fa09343ec954f8abebcac878c
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

Loading…