Benzoic Acid → diethyl [1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]methylmalonate

HRID 350025Notes

Reaction equation

HRID 350025 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:33]=[CH:32][C:18]([CH2:19][N:20]2[CH:24]=[C:23]([CH:25]=O)[C:22]([C:27]3[S:28][CH:29]=[CH:30][CH:31]=3)=[N:21]2)=[CH:17][CH:16]=1.[C:34]([O:42][CH2:43][CH3:44])(=[O:41])[CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37].N1CCCCC1.C(O)(=O)C1C=CC=CC=1.Cl>C1(C)C=CC=CC=1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:33]=[CH:32][C:18]([CH2:19][N:20]2[CH:24]=[C:23]([CH2:25][CH:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:34]([O:42][CH2:43][CH3:44])=[O:41])[C:22]([C:27]3[S:28][CH:29]=[CH:30][CH:31]=3)=[N:21]2)=[CH:17][CH:16]=1

Participants

7

Reactant 5

HCID 243Benzoic AcidHCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 8082PiperidineHCID 230248961-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazole-4-carbaldehyde

Product 1

HCID 70125202diethyl [1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]methylmalonateYield 92%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazole-4-carbaldehyde (5.02 g), diethyl malonate (2.12 g), piperidine (0.35 ml), benzoic acid (0.27 g), and toluene (50 ml) was subjected to azeotropic dehydration for 1 hour. The reaction mixture was poured into dilute hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel-chromatography to obtain a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). Sodium borohydride (170 mg) was added to a mixture of the obtained colorless oily substance, ethanol (20 ml), and tetrahydrofuran (20 ml) at 0° C., and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into dilute hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel chromatography to obtain diethyl [1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]methylmalonate (6.08 g, yield: 92%) as a pale yellow oily substance from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto obtain a colorless oily substance from the fraction
  6. washeluted with ethyl acetate-hexane (1:2, volume ratio)
  7. additionSodium borohydride (170 mg) was added to a mixture of the obtained colorless oily substance, ethanol (20 ml), and tetrahydrofuran (20 ml) at 0° C.
  8. additionThe reaction mixture was poured into dilute hydrochloric acid
  9. extractionextracted with ethyl acetate
  10. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-f7f854388e1245c6ad8e1838745a97df
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

Loading…