تفاعل #1117707

معادلة التفاعل

2-bromopyridine

N-t-butoxycarbonyl-L-leucinal

n-butyl lithium

→

( S )

المردود 21.6%

2-tert-butoxycarbonylamino-4-methyl-(R)1-(2-pyridinyl)pentan-1-ol

المردود 21.6%

المذيبات

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThe mixture was stirred for 35 minutes
2. 2
   أخرىquenched with 10 ml of saturated sodium sulfate solution
3. 3
   workup.ADDITIONpoured into 50 ml of water
4. 4
   استخلاصThe mixture was extracted with ethyl acetate
5. 5
   تجفيفThe extract was dried (Na2SO4)
6. 6
   أخرىthe solvent removed under vacuum
7. 7
   أخرىThe residue was chromatographed over silica gel with ethyl acetatheexane (3:7) as eluent

الإجراء التجريبي

To 2-bromopyridine (3.16 g) in 20 ml of dry tetrahydrofuran cooled to -78° C. under argon was added slowly 11.2 ml of n-butyl lithium in tetrahydrofuran (2M). The solution was stirred for 5 minutes and then 2.1 g of N-t-butoxycarbonyl-L-leucinal in 10 ml of tetrahydrofuran was added. The mixture was stirred for 35 minutes, then quenched with 10 ml of saturated sodium sulfate solution, warmed to room temperature and poured into 50 ml of water. The mixture was extracted with ethyl acetate. The extract was dried (Na2SO4) and the solvent removed under vacuum. The residue was chromatographed over silica gel with ethyl acetatheexane (3:7) as eluent and then ethyl acetate-hexane (1:1) as eluent to give 0.62 g of (S) 2-tert-butoxycarbonyl-amino-4-methyl(R,S)1-(2-pyridinyl)pentan-1-ol as a yellow oil; [α]D26 -21°±3° (C, 0.329, dichloromethane). A4.12 sample of the preceding compound in a mixture of 15 ml of dichloromethane and 5 ml of acetic anhydride was stirred at room temperature for 22 hours. The mixture was concentrated under vacuum. The residue was dissolved in dichloromethane and the solution washed with saturated agneous sodium carbonate, dried (Na2SO4) and the solvent removed. The residue was chromatographed over silica gel with 30% ethyl acetate in hexane to give 1.55 g of (S) 2-tert-butoxycarbonylamino-4-methyl-(S)1-(2-pyridinyl)pentan-1-ol, 0-acetate as crystals, mp 83°-84° C.; [α]D26 -62°±1° (C. 1.01, dichloromethane) and (S) 2-tert-butoxycarbonylamino-4-methyl-(R)1-(2-pyridinyl)pentan-1-ol, 0-acetate as an amber oil; [α]D26 +3°±1° (C, 1.-66, methanol).

المصدر