4-Chlorotoluene → 4-Morpholinobenzonitrile

温度

100 °C

Amination using 0.05 mol % Pd. An oven-dried resealable Schlenk tube was purged with argon and charged with Pd2(dba)3 (2.3 mg, 0.0025 mmol, 0.05 mol % Pd), ligand 2 (2.9 mg, 0.0075 mmol, 0.075 mol %), and NaOt-Bu (1.34 g, 13.9 mmol). Toluene (10 mL), di-n-butylamine (2.00 mL, 11.9 mmol), and 4-chlorotoluene (1.18 mL, 10.0 mmol) were added and the mixture was degassed using three freeze-pump-thaw cycles. The reaction vessel was placed under argon, sealed with a teflon screw cap, and stirred in a 100° C. oil bath for 20 h after which time GC analysis showed the aryl halide had been completely consumed. The reaction mixture was cooled to room temperature, diluted with ether (100 mL) and extracted with 1 M HCl (3×100 mL). The combined aqueous acid phase was basified with 3N NaOH, then extracted with ether (3×150 mL). The ethereal extracts were dried over anhydrous sodium sulfate, filtered and concentrated to afford 2.01 g (95%) of di-n-butyltoluidine6 as a pale yellow oil. General procedure for the room-temperature palladium-catalyzed amination of aryl bromides: An oven-dried resealable Schlenk tube was purged with argon and charged with Pd2(dba)3 (0.005-0.025 mmol, 1-5 mol % Pd), ligand 2 (0.015-0.075 mmol, 1.5-7.5 mol %), and NaOt-Bu (1.4 mmol) [see Table 1 for amount of Pd and ligand used]. The tube was purged with argon, fitted with a rubber septum and then DME (0.5 mL-1.0 mL), the aryl bromide (1.0 mmol) and the amine (1.2 mmol) were added via syringe. The septum was removed, the tube was sealed with a teflon screw cap and the mixture was stirred at room temperature for 24 h. The reaction mixture was then diluted with ether (20 mL), filtered through celite and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel.

1. customAn oven-dried resealable Schlenk tube was purged with argon
2. customthe mixture was degassed
3. customsealed with a teflon
4. customscrew cap
5. customhad been completely consumed
6. temperatureThe reaction mixture was cooled to room temperature
7. additiondiluted with ether (100 mL)
8. extractionextracted with 1 M HCl (3×100 mL)
9. extractionextracted with ether (3×150 mL)
10. dry with materialThe ethereal extracts were dried over anhydrous sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customto afford 2.01 g (95%) of di-n-butyltoluidine6 as a pale yellow oil
14. customAn oven-dried resealable Schlenk tube was purged with argon
15. customThe tube was purged with argon
16. customfitted with a rubber septum
17. customThe septum was removed
18. customthe tube was sealed with a teflon
19. customscrew cap
20. stirringthe mixture was stirred at room temperature for 24 h
21. additionThe reaction mixture was then diluted with ether (20 mL)
22. filtrationfiltered through celite and
23. concentrationconcentrated in vacuo
24. customThe crude material was purified by flash chromatography on silica gel

ORDレコード

ord-86f7a141f5c14cc5831466781fb14693

出典データセット

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07560582B2