تفاعل #563981

معادلة التفاعل

N-[(1,1-dimethylethoxy)carbonyl]-L-leucinal

n-Butyllithium

thiazole

→

(2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methyl-1-(2-thiazolyl)-1-pentanol

المذيبات

tetrahydrofuran

hexane

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooled to -70° under argon
2. 2
   درجة الحرارةAfter cooling
3. 3
   أخرىthe reaction to -50°
4. 4
   workup.ADDITIONis added
5. 5
   درجة الحرارةAfter 90 minutes the reaction is warmed to -10°
6. 6
   أخرىquenched with saturated ammonium chloride (10 ml.)
7. 7
   استخلاصThe reaction mixture is extracted into ether
8. 8
   استخلاصthe organic extract
9. 9
   غسيلis rinsed with water and brine, dired (MgSO4)
10. 10
    تركيزconcentrated in vacuo
11. 11
    أخرىto give 1.8 g
12. 12
    غسيلof silica gel (LPS-1) eluting with petroleum ether:acetone (20:1 )
13. 13
    أخرىto remove a minor impurity from the co-eluting desired diastereimeric product mixture

الإجراء التجريبي

2.5 n-Butyllithium in hexane (8 ml.) is added to a solution containing thiazole (1.7 g., 20 mmole) in dry tetrahydrofuran (60 ml.) cooled to -70° under argon. After stirring a short time, the solid material begins to come out of solution. The reaction remains heterogeneous after 35 minutes at -40° to -35° . After cooling the reaction to -50° , a solution containing N-[(1,1-dimethylethoxy)carbonyl]-L-leucinal (2.2g., 10 mmole) in tetrahydrofuran (5 ml.) is added. After 90 minutes the reaction is warmed to -10° and quenched with saturated ammonium chloride (10 ml.). The reaction mixture is extracted into ether and the organic extract is rinsed with water and brine, dired (MgSO4) and concentrated in vacuo to give 1.8 g. of amide product. Two flash chromatographies on first 100 g. and then 150 g. of silica gel (LPS-1) eluting with petroleum ether:acetone (20:1 ) fails to remove a minor impurity from the co-eluting desired diastereimeric product mixture. A total of 1.2 g. of (2S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methyl-1-(2-thiazolyl)-1-pentanol is obtained. TLC (silica gel; petroleum ether:acetone, 4:1) Rf =0.37. 8 α]D =-38.6° (c=1, chloroform).

المصدر