Sodium Cyanide → 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,3-trimethylbutanoic acid

HRID 218174Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([CH3:26])([CH3:25])[C:18]([CH3:24])([CH3:23])[C:19]([O:21]C)=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[I-].[Li+].[C-]#N.[Na+]>N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]([CH3:26])([CH3:25])[C:18]([CH3:24])([CH3:23])[C:19]([OH:21])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 170 °C

Procedure

A mixture of methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,3-trimethylbutanoate (330 mg, 0.93 mmol), lithium iodide (500 mg, 3.7 mmol), sodium cyanide (180 mg, 3.7 mmol), and pyridine (3 mL) was heated in CEM Explorer microwave reactor under nitrogen at 170° C. for 30 min. The reaction mixture was concentrated in vacuo, mixed with water (10 mL) and ethyl acetate (10 mL), and acidified with 10% aqueous citric acid solution to pH=4. The aqueous layer was separated and extracted with ethyl acetate (2×10 mL). The combined organic solutions were dried (Na2SO4) and concentrated to give 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2,3-trimethylbutanoic acid (310 mg, 0.91 mmol, 98% yield) that was used as such for the subsequent step without further purification.

Workup

concentrationThe reaction mixture was concentrated in vacuo
additionmixed with water (10 mL) and ethyl acetate (10 mL)
customThe aqueous layer was separated
extractionextracted with ethyl acetate (2×10 mL)
dry with materialThe combined organic solutions were dried (Na2SO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-412707e0f04c4898ac803fd0276d12e3
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08198311B2

Reaction notes

Loading…