Hydrochloric Acid → {1-[4-(1-Hydroxy-2-phenyl-ethyl)-benzyl]-3,5-dimethyl-1H-pyrazol-4-yl}-acetic acid methyl ester

HRID 1631923Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:21])[CH2:4][C:5]1[C:6]([CH3:20])=[N:7][N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([CH:18]=[O:19])=[CH:14][CH:13]=2)[C:9]=1[CH3:10].[CH2:22]([Mg]Cl)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.Cl>O1CCCC1>[CH3:1][O:2][C:3](=[O:21])[CH2:4][C:5]1[C:6]([CH3:20])=[N:7][N:8]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([CH:18]([OH:19])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:16][CH:17]=2)[C:9]=1[CH3:10]

Participants

Conditions

Temperature: -78 °C

Procedure

[1-(4-Formyl-benzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-acetic acid methyl ester (intermediate 15.1.1, 500 mg, 1.8 mmol) was dissolved in 5 ml tetrahydrofuran, cooled to −78° C., and benzyl magnesium chloride (1.92 ml, 2 M solution in tetrahydrofuran) was added to the solution. After 30 min at this temperature, the mixture was warmed to room temperature within 12 h, and ice and 4 N aqueous HCl was added to the solution. After dilution with ethyl acetate, the organic layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by MPLC (silica gel, CH2Cl2/methanol 98:2).

Workup

temperaturethe mixture was warmed to room temperature within 12 h
customAfter dilution with ethyl acetate, the organic layer was separated
extractionthe aqueous layer was extracted twice with ethyl acetate
dry with materialThe combined organic layer was dried over MgSO4
customthe solvent was removed under reduced pressure
customThe residue was purified by MPLC (silica gel, CH2Cl2/methanol 98:2)

Sources & evidence

ORD record: ord-26cb8e164ab5402485546a06b97c10cd
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791272B2

Reaction notes

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