Isopropyl chloroformate → 5-[1-(1-Methyl-1H-indol-3-yl)-2,2,2-trifluoro-1-hydroxyethyl]indazole-1-carboxylic acid isopropyl ester

HRID 244419Notes

Reaction equation

[F:1][C:2]([F:25])([F:24])[C:3]([C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][N:19]=[CH:18]2)([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH3:14])[CH:6]=1)[OH:4].Cl[C:27]([O:29][CH:30]([CH3:32])[CH3:31])=[O:28]>C1(C)C=CC=CC=1.N1C=CC=CC=1.CCOCC.O>[CH:30]([O:29][C:27]([N:20]1[C:21]2[C:17](=[CH:16][C:15]([C:3]([C:5]3[C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[N:7]([CH3:14])[CH:6]=3)([OH:4])[C:2]([F:1])([F:24])[F:25])=[CH:23][CH:22]=2)[CH:18]=[N:19]1)=[O:28])([CH3:32])[CH3:31]

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 2,2,2-trifluoro-1-(1H-indazol-5-yl)-1-(1-methyl-1H-indol-3-yl)ethanol (0.165 mmol) and isopropyl chloroformate (0.49 mmol from a 1.0 M solution in toluene) in 1 mL of pyridine was heated at 85° C. for 10 hours, cooled to room temperature, and diluted with ether and water. The organic layer was washed with water and brine and dried over magnesium sulfate. The volatiles were concentrated in vacuo and the residue purified by flash silica gel chromatography using 33% ethyl acetate in hexanes. The product-rich fractions were concentrated in vacuo to afford 0.069 mmol of the desired compound, m.p. 105° C.-106° C.

Workup

temperaturecooled to room temperature
washThe organic layer was washed with water and brine
dry with materialdried over magnesium sulfate
concentrationThe volatiles were concentrated in vacuo
customthe residue purified by flash silica gel chromatography
concentrationThe product-rich fractions were concentrated in vacuo

Sources & evidence

ORD record: ord-4f6c81ff658b4ff0aca55d9b1ba68360
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658637B2

Reaction notes

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