Diiodomethane → 5-Iodo-4'-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide

A mixture of 5-amino-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide (5.3 g, 17. 8 mmol), iso-amyl nitrite (13.5 ml, 88.9 mmol) and diiodomethane (8 ml, 106.7 mmol) was stirred at room temperature for 1 hour. The mixture was then heated to 65 ° C. and kept for 8 hours, LC/MS indicated that reaction completed. The reaction mixture was cooled to room temperature and the separation of iodobenzene from excess diiodomethane was effected by addition of the reaction mixture at room temperature to a stirred solution of piperidin-CH3CN (V/V=90 ml/90 ml). A vigorous exothermic reaction ensued. The excess volatile reagents were removed by rotary evaporation at 80° C. The residue was diluted with ethyl acetate, washed with 10% hydrochloric acid, water and brine. The organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (ethyl acetate/hexanes=10:1) to yield 5-iodo-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide as a yellow solid (5.2 g, 83.8%). MS (M+H)=410.

1. temperatureThe mixture was then heated to 65 ° C.
2. waitkept for 8 hours
3. customLC/MS indicated that reaction
4. temperatureThe reaction mixture was cooled to room temperature
5. customthe separation of iodobenzene from excess diiodomethane
6. additionwas effected by addition of the reaction mixture at room temperature to a stirred solution of piperidin-CH3CN (V/V=90 ml/90 ml)
7. customA vigorous exothermic reaction
8. customThe excess volatile reagents were removed by rotary evaporation at 80° C
9. additionThe residue was diluted with ethyl acetate
10. washwashed with 10% hydrochloric acid, water and brine
11. customThe organic layer was separated
12. dry with materialdried over anhydrous Na2SO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe residue was purified by flash column chromatography (ethyl acetate/hexanes=10:1)

ORD 기록

ord-3af8fc9d88cc40c6971948105b84ab7e

출처 데이터셋

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09173861B2