Water → Methyl 6-(trifluoromethyl)-1H-indazole-3-carboxylate

HRID 2108945Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:19])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:6]=1[NH:15]C(=O)C.[N:20](OC(C)(C)C)=O.O>C(O)(=O)C>[CH3:1][O:2][C:3]([C:4]1[C:5]2[C:6](=[CH:7][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:9][CH:10]=2)[NH:15][N:20]=1)=[O:19]

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of (2-acetylamino-4-trifluoromethylphenyl)-acetic acid methyl ester (16 g, 0.058 mol) in acetic acid (50 mL) was added dropwise t-butyl nitrite (90%) (7.35 g, 0.063 mol) over a period of 20 min. at 90-95° C. The mixture was then stirred for 0.5 h at 95° C., poured into cold water and stirred for 1 h. The precipitates were collected by filtration and washed with water. The crude material was dissolved in ethyl acetate and dried over sodium sulfate. The solvent was removed in vacuo. This material (13.4 g, 95%) was used without further purification in the next step. A small sample was crystallized from ethyl acetate to yield a white solid, mp 240-242° C. 1H NMR (DMSO-d-6) 8.25 (d, J=8.5 Hz, 1H), 8.04 (s, 1H), 7.58 (d, J=8.5 Hz, 1H), 3.95 (s, 3H). MS (FAB) m/z: 245.1 (M++1).

Workup

stirringstirred for 1 h
filtrationThe precipitates were collected by filtration
washwashed with water
dissolutionThe crude material was dissolved in ethyl acetate
dry with materialdried over sodium sulfate
customThe solvent was removed in vacuo
customThis material (13.4 g, 95%) was used without further purification in the next step
customA small sample was crystallized from ethyl acetate
customto yield a white solid, mp 240-242° C

Sources & evidence

ORD record: ord-d637fa0db9114d579861c5e83b4f1477
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07514463B2

Reaction notes

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