Hydrochloric Acid → 3-[1-[4-[5-methyl-2-(4-pyridyl)-4-oxazolylmethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid

HRID 350104Notes

Reaction equation

HRID 350104 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[OH:13][C:14]1[CH:37]=[CH:36][C:17]([CH2:18][N:19]2[CH:23]=[C:22]([CH2:24][CH2:25][C:26]([O:28]C)=[O:27])[C:21]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:20]2)=[CH:16][CH:15]=1.[CH3:38][C:39]1[O:43][C:42]([C:44]2[CH:49]=[CH:48][N:47]=[CH:46][CH:45]=2)=[N:41][C:40]=1[CH2:50]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.[OH-].[Li+].Cl>CO.O.O1CCCC1>[CH3:38][C:39]1[O:43][C:42]([C:44]2[CH:49]=[CH:48][N:47]=[CH:46][CH:45]=2)=[N:41][C:40]=1[CH2:50][O:13][C:14]1[CH:37]=[CH:36][C:17]([CH2:18][N:19]2[CH:23]=[C:22]([CH2:24][CH2:25][C:26]([OH:28])=[O:27])[C:21]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)=[N:20]2)=[CH:16][CH:15]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 168937Lithium hydroxide, monohydrateHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 23024942[5-Methyl-2-(4-pyridyl)-4-oxazolyl]methanolHCID 23024960methyl 3-[1-(4-hydroxybenzyl)-3-phenyl-1H-pyrazol-4-yl]propionate

Product 1

HCID 694215373-[1-[4-[5-methyl-2-(4-pyridyl)-4-oxazolylmethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acidYield 68%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Diethyl azodicarboxylate (40% in toluene, 753 mg) was added dropwise slowly to a mixture of methyl 3-[1-(4-hydroxybenzyl)-3-phenyl-1H-pyrazol-4-yl]propionate (500 mg), [5-methyl-2-(4-pyridyl)-4-oxazolyl]methanol (274 mg), triphenylphosphine (414 mg) and tetrahydrofuran (7 ml) at room temperature. After stirring at room temperature for 4 hours, the reaction solvent was removed under reduced pressure. The residue was subjected to silica gel column chromatography, and an oily substance was obtained from the fraction eluted with ethyl acetate-hexane (3:1, volume ratio). A mixture of the oily substance obtained, lithium hydroxide monohydrate (181 mg), tetrahydrofuran (6 ml), water (4 ml) and methanol (4 ml) was stirred at room temperature for 2 hours, and 1N hydrochloric acid (4.3 ml) was added to the mixture, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The colorless crystals obtained were collected by filtration to yield 3-[1-[4-[5-methyl-2-(4-pyridyl)-4-oxazolylmethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid (470 mg, yield: 68%). This was recrystallized from tetrahydrofuran-hexane. Melting point: 154–155° C.

Workup

  1. customthe reaction solvent was removed under reduced pressure
  2. customan oily substance was obtained from the fraction
  3. washeluted with ethyl acetate-hexane (3:1, volume ratio)
  4. additionA mixture of the oily substance
  5. customobtained
  6. extractionwas extracted with ethyl acetate
  7. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride solution
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe colorless crystals obtained
  11. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-17f81e8c170e44ad8eca44c7a20fd52f
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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