4-Iodo-5-methylisoxazole → 2-Chloro-4-(5-methylisoxazol-4-yl)aniline

HRID 2205904Notes

Reaction equation

I[C:2]1[CH:3]=[N:4][O:5][C:6]=1[CH3:7].[Cl:8][C:9]1[CH:15]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:13]=[CH:12][C:10]=1[NH2:11]>COCCOC.O.CCOC(C)=O>[Cl:8][C:9]1[CH:15]=[C:14]([C:2]2[CH:3]=[N:4][O:5][C:6]=2[CH3:7])[CH:13]=[CH:12][C:10]=1[NH2:11]

Participants

Conditions

Temperature: 80 °C

Procedure

Prepared according to Method B (Preparation 83) using 4-iodo-5-methylisoxazole and 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline in DME/H2O 1/1 (1.4 mL). The reaction mixture was stirred at 80° C. for 7 hours before being diluted with EtOAc and quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude mixture was purified using Biotage silica gel column chromatography eluting with Cyclohexane/EtOAc 99/1 to 80/20 to give the title product as a colourless oil (36 mg, 44%). 1H NMR (500 MHz, CDCl3): δ 2.54 (s, 3H), 4.16 (br s, 2H), 6.83 (d, J=8.2 Hz, 1H), 7.09 (dd, J=8.2, 2.0 Hz, 1H), 7.27 (d, J=2.0 Hz, 1H), 8.28 (s, 1H).

Workup

customPrepared
customaccording to Method B (Preparation 83)
customquenched with water
customThe layers were separated
extractionthe aqueous layer was extracted with EtOAc
dry with materialThe combined organic layers were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude mixture was purified
washeluting with Cyclohexane/EtOAc 99/1 to 80/20

Sources & evidence

ORD record: ord-1cfea2b75077420f9e3c4f411e2589d2
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371319B2

Reaction notes

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