Ethyl Acetate → 3-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine

HRID 919459Notes

Reaction equation

[F:1][C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:12]=[C:11]([N+:13]([O-])=O)[CH:10]=[CH:9][C:8]=1[O:16][CH3:17].[OH-].[Na+].CCOC(C)=O>CCO>[F:1][C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:12]=[C:11]([NH2:13])[CH:10]=[CH:9][C:8]=1[O:16][CH3:17]

Participants

Conditions

Temperature: 50 °C

Procedure

4-Fluoro-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole (205 mg, 0.817 mmol) in EtOH (25 mL) was treated with Sn(II) chloride dihydrate (626.3 mg, 2.45 mmol) and heated to 50° C. for 12 hours. The reaction was allowed to cool to room temperature and 10% NaOH (100 ml) was added. EtOAc (50 ml) was added and the organic layer was separated. The aqueous layer was extracted with EtOAc (2×50 mL) and the organics combined, dried over Na2SO4, filtered, and the solvent removed under reduced pressure. The residue was dissolved in DMSO (5 ml), and purified by preparative HPLC to afford 85 mg (47%) of 3-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine as a light brown oil. LCMS m/z (%)=222 (M+H, 100). 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, JH,F=4.8 Hz, 1H), 6.86 (d, J=8.8 Hz, 1H), 6.79 (dd, J1=8.8 Hz, J2=2.8 Hz, 1H), 6.64 (d, J=2.8 Hz, 1H), 3.75 (s, 3H), 3.69 (s, 3H), 3.21 (s, 2H). 19F NMR (376 MHz, CDCl3) δ: −175.50 (d, JH,F=5.3 Hz, 1F).

Workup

temperatureto cool to room temperature
customthe organic layer was separated
extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
dry with materialdried over Na2SO4
filtrationfiltered
customthe solvent removed under reduced pressure
dissolutionThe residue was dissolved in DMSO (5 ml)
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-1a2bc199c45e4108aac868b1c05a1813
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273035B2

Reaction notes

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