反応 #80846

反応方程式

magnesium

2-cyanopyridine

cyclohexylmethyl bromide

sodium borohydride

→

1-(R,S)-(2-pyridyl)-2-cyclohexylethylamine

収率 75.0%

溶媒

t-butylmethyl ether

MTBE

MTBE

methanol

反応条件

後処理

1. 1
   温度heating
2. 2
   workup.ADDITIONthe remainder of the solution was added at a rate
3. 3
   温度to maintain
4. 4
   温度refluxing temperature
5. 5
   workup.ADDITIONAfter the addition
6. 6
   温度the reaction was refluxed for an additional 24 hrs
7. 7
   温度cooled to 0° to 5° C.
8. 8
   workup.ADDITIONAfter the addition
9. 9
   workup.STIRRINGthe greenish thick suspension was stirred
10. 10
    温度without cooling for 18-24 hrs
11. 11
    その他The Grignard reaction mixture
12. 12
    workup.STIRRINGThe mixture was stirred at room temperature 18 hrs
13. 13
    その他, then quenched by the addition of 16 L of water and 36 L of 4N hydrochloric acid
14. 14
    その他The organic solvents were removed under vacuum
15. 15
    洗浄the remaining aqueous solution was washed twice with 6 L of methylene chloride
16. 16
    抽出extracted three times with 10 L of methylene chloride
17. 17
    乾燥The methylene chloride was dried over 6.5 kg of sodium sulfate
18. 18
    濃縮concentrated

実験手順

To a refluxed stirred mixture of 1.34 kg (55.8 moles) of magnesium in 6 L of t-butylmethyl ether (MTBE) and 4 g (0.016 moles) of iodine, a solution of 10 kg (55.9 moles) cyclohexylmethyl bromide in 22 L (MTBE) was added slowly. After approximately 10% to 25% of the solution was added, heating was discontinued and the remainder of the solution was added at a rate to maintain refluxing temperature. After the addition, the reaction was refluxed for an additional 24 hrs, then cooled to 0° to 5° C. and 3.903 kg (37.1 moles) of 2-cyanopyridine in 22 L MTBE was added at 0°-10° C. After the addition, the greenish thick suspension was stirred without cooling for 18-24 hrs. The Grignard reaction mixture was transferred with stirring to 40 L of methanol at 10° to 15° C. To the clear solution was added 1.4 kg (36.8 moles) of sodium borohydride. The mixture was stirred at room temperature 18 hrs., then quenched by the addition of 16 L of water and 36 L of 4N hydrochloric acid. The organic solvents were removed under vacuum and the remaining aqueous solution was washed twice with 6 L of methylene chloride. The aqueous phase was basified with 15 L of ammonium hydroxide solution and extracted three times with 10 L of methylene chloride. The methylene chloride was dried over 6.5 kg of sodium sulfate and concentrated to yield 5.645 kg (75%) of 1-(R,S)-(2-pyridyl)-2-cyclohexylethylamine.

出典