Acetic Acid → 5-chloro-1-(3-methoxypropyl)-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 12908Notes

Reaction equation

HRID 12908 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([CH2:12][CH2:13][CH2:14][O:15][CH3:16])[C:10]=1N)=[O:5])[CH3:2].C(O)(=O)C.N(OC(C)(C)C)=O.[ClH:28]>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([CH2:12][CH2:13][CH2:14][O:15][CH3:16])[C:10]=1[Cl:28])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 67020934HCID 67020934, compound

Product 1

HCID 670209005-chloro-1-(3-methoxypropyl)-1H-pyrazole-4-carboxylic acid ethyl esterYield 30%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 5-amino-1-(3-methoxypropyl)-1H-pyrazole-4-carboxylic acid ethyl ester (5.22 g, 23.0 mmol) in dry acetonitrile (46 mL) was added anhydrous cuprous chloride (3.73 g, 37.7 mmol) and acetic acid (2.6 mL, 46.0 mmol). The mixture was cooled to 0° C. in an ice-water bath after which tert-butyl nitrite (4.9 mL, 36.8 mmol) was added over 10 minutes. The solution was allowed to warm to room temperature and stir for 4 h. To the solution was carefully added 6.0N hydrochloric acid (20 mL). The aqueous layer was extracted with methylene chloride (2×100 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to provide the crude material. The product was purified by column chromatography on silica gel (eluting with ethyl acetate/hexanes, 1:1) to provide 5-chloro-1-(3-methoxypropyl)-1H-pyrazole-4-carboxylic acid ethyl ester (1.71 g, 30%) as an orange oil. Mass spectrum: m/z: 247.3 (M+1).

Workup

  1. additionwas added over 10 minutes
  2. extractionThe aqueous layer was extracted with methylene chloride (2×100 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide the crude material
  7. customThe product was purified by column chromatography on silica gel (eluting with ethyl acetate/hexanes, 1:1)

Sources & evidence

ORD record
ord-fe6d3944e1c5450b873a447ab77c6fba
Source dataset
uspto-grants-2010_06
Patent number
US07728029B2

Reaction notes

Loading…