Methyl 2-amino-5-iodo-4-(trifluoromethyl)benzoate → 2-Amino-4-trifluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester

HRID 906574Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](I)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15].[CH:17]([N:20]1[C:24]([Sn](CCCC)(CCCC)CCCC)=[CH:23][CH:22]=[N:21]1)([CH3:19])[CH3:18]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:24]2[N:20]([CH:17]([CH3:19])[CH3:18])[N:21]=[CH:22][CH:23]=2)[C:7]([C:11]([F:14])([F:13])[F:12])=[CH:6][C:5]=1[NH2:15]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-amino-4-trifluoromethyl-5-iodo-benzoic acid methyl ester (1.56 g, 4.52 mmol) in dioxane (40 mL) were added 1-isopropyl-5-tributylstannanyl-1H-pyrazole (2.34 g, 1.3 eq) and Pd(dppf)2Cl2 (369 mg, 0.1 eq) and the resulting mixture was stirred at 100° C. for 18 h. A second portion of catalyst (0.1 eq) was added and the mixture was stirred at 100° C. for 24 h. A last portion of catalyst (0.1 equiv) was added and the mixture was kept at 100° C. for 72 h. The solvent was removed in vacuo to provide a dark oil which was purified by flash chromatography (silica gel, EtOAc/hexanes (0:100 to 50:50)) to give the title compound (666 mg, 45%) as an off-white solid (ES-MS: m/z 328.3 [M+H]+, rt 5.60 min).

Workup

stirringthe mixture was stirred at 100° C. for 24 h
waitthe mixture was kept at 100° C. for 72 h
customThe solvent was removed in vacuo
customto provide a dark oil which
customwas purified by flash chromatography (silica gel, EtOAc/hexanes (0:100 to 50:50))

Sources & evidence

ORD record: ord-e3037ceb79d94fb0b1e03c2afc8f9793
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012988B2

Reaction notes

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