1,4-Dioxane → 2-amino-4-ethyl-5-(2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester

HRID 906602

Reaction equation

[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8](I)[C:7]([CH2:11][CH3:12])=[CH:6][C:5]=1[NH2:13].[CH3:15][N:16]1[C:20]([Sn](CCCC)(CCCC)CCCC)=[CH:19][CH:18]=[N:17]1.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].CCOC(C)=O>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([C:20]2[N:16]([CH3:15])[N:17]=[CH:18][CH:19]=2)[C:7]([CH2:11][CH3:12])=[CH:6][C:5]=1[NH2:13]

Participants

Conditions

Temperature: 100 °C

Procedure

2-Amino-5-iodo-4-ethyl-benzoic acid methyl ester (280 mg, 0.92 mmol) and 1-methyl-5-tributylstannanyl-1H-pyrazole (409 mg, 1.2 equiv) were weighed in air and added to a flame-dried flask. [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium (75 mg, 0.1 equiv) was added and the flask was closed by a septum. Dioxane (1 mL) was added and the mixture was stirred at 100° C. for 18 h (TLC control). The mixture was dissolved with EtOAc, filtered and evaporated to dryness. The crude product was purified by flash chromatography (hexanes to EtOAc/hexanes (4:6)) to yield 2-amino-4-ethyl-5-(2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (163 mg, 68% yield) as a yellow solid. ESI-MS: m/z 260.3 [M+H]+, rt 6.37 min.

Workup

additionadded to a flame-dried flask
customthe flask was closed by a septum
filtrationfiltered
customevaporated to dryness
customThe crude product was purified by flash chromatography (hexanes to EtOAc/hexanes (4:6))

Sources & evidence

ORD record: ord-139aa7e9fc524e31ab2a94840ad9736e
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012988B2

Linked notes

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