Hydrochloric Acid → 1-benzyl-5-methyl-1H-pyrazole-4-carboxylic acid

HRID 2206459Notes

Reaction equation

[CH2:1]([N:8]1[C:12]([CH3:13])=[C:11]([C:14]([O:16]C)=[O:15])[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+].O1CCCC1.Cl>O.CO>[CH2:1]([N:8]1[C:12]([CH3:13])=[C:11]([C:14]([OH:16])=[O:15])[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 20 °C

Procedure

A mixture of methyl 1-benzyl-5-methyl-1H-pyrazole-4-carboxylate (200 mg, 0.86 mmol), lithium hydroxide monohydrate (111 mg, 2.62 mmol), tetrahydrofuran (10 mL), methanol (2 mL) and water (2 mL) was stirred at 20° C. for 4 hours. The mixture was acidified to pH=1 with concentrated hydrochloric acid and then extracted with ethyl acetate (15 mL×3). The combined organic phase was dried by sodium sulfate, and then filtered. The filtrate was concentrated in vacuo and separated by chiral HPLC (condition: column AD-H (20 mm*250 mm*5 μm), hexane: ethanol (0.2% DEA)=50:50, flow rate: 13 mL/min) to give 1-benzyl-5-methyl-1H-pyrazole-4-carboxylic acid (75 mg, 40%). LRMS (M+H+) m/z: calcd. 216.09. found 216.

Workup

extractionextracted with ethyl acetate (15 mL×3)
dry with materialThe combined organic phase was dried by sodium sulfate
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo
customseparated by chiral HPLC (condition: column AD-H (20 mm*250 mm*5 μm), hexane: ethanol (0.2% DEA)=50:50, flow rate: 13 mL/min)

Sources & evidence

ORD record: ord-5303fb3f1a134a3f9b640c92bf9cef1b
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371331B2

Reaction notes

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