1-Methylpyrrole → 3-(1-methyl-1H-pyrrol-2-yl)benzaldehyde

Temperature

-78 °C

EX-602A) To solution of N-methylpyrrole (0.97 mL, 11 mmol) in Et2O (20 mL) was added neat TMEDA (1.5 mL, 10 mmol) and 1.6 M n-BuLi in hexanes (6.3 mL, 10 mmol). The solution was heated to reflux under N2 for 1 h and then cooled to −78° C. A 1.0 M solution of Me3SnCl in THF was added over 15 min, and the resulting solution stirred for 30 min at −78° C. After warming to room temperature, 3-bromo-benzaldehyde (0.70 mL, 6.0 mmol), Pd(PPh3)2Cl2 (0.25 g, 0.35 mmol) and dioxane (10 mL) were added. The slurry was heated to reflux for 18 h. The cooled mixture was poured into a mixture of saturated KF and ethyl acetate and stirred 15 min. The slurry was filtered through celite. The organic layer was separated, washed with brine, dried (MgSO4) and evaporated to an oil. Purification by flash chromatography on silica gel eluting with 5% ethyl acetate in hexane gave 0.45 g (24%) of the desired 3-(1-methyl-1H-pyrrol-2-yl)benzaldehyde product as a yellow oil. MS: m/z=186.2 [M+H]+. EX-602B) To a 1.2-dichloroethane (10 mL) solution of aldehyde (0.45 g, 2.4 mmol) from EX-602A was added 3-phenoxyaniline (0.45 g, 2.4 mmol), NaB(OAc)3H (0.67 g, 3.2 mmol) and acetic acid (0.15 mL, 2.4 mmol). The cloudy solution was stirred at room temperature for 2 h. The reaction mixture was poured into water and extracted with dichloromethane. The organic layer was washed with saturated NaHCO3 and brine, dried (MgSO4) and evaporated to yield 0.67 g (79%) of the desired N-(3-phenoxyphenyl)[[3-(1-methyl-1H-pyrrol-2-yl)phenyl]methyl]amine product as a yellow oil which was used without further purification. 1H NMR (CDCl3) δ3.60 (s, 3H), 4.15 (br s, 1H), 4.35 (s, 2H), 6.2-6.4 (m, 5H), 6.67 (s, 1H), 7.00-7.05 (m, 4H), 7.1-7.2 (m, 6H). The formation of the desired product was monitored by the disappearance of the aldehyde peak (δ˜10) and the formation of the benzyl peak (δ4.35) in the 1H NMR spectrum.

1. temperatureThe solution was heated
2. temperatureto reflux under N2 for 1 h
3. temperatureAfter warming to room temperature
4. temperatureThe slurry was heated
5. temperatureto reflux for 18 h
6. stirringstirred 15 min
7. filtrationThe slurry was filtered through celite
8. customThe organic layer was separated
9. washwashed with brine
10. dry with materialdried (MgSO4)
11. customevaporated to an oil
12. customPurification by flash chromatography on silica gel eluting with 5% ethyl acetate in hexane

ORD record

ord-37854c256d8b483d929a318bb909a35a

Source dataset

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06476075B1