Réaction #6532

Équation de réaction

3-Pyridinecarboxaldehyde

dibutylboron triflate

diisopropylethylamine

→

(2S)-2-[(1S-1-hydroxy-1-(3-pyridyl)methyl]pent-4-enoyl)-4-isopropyloxazolidin-2-one

2-allyl-1-(3-pyridyl)-1,3-propanediol

Solvants

dichloromethane

dichloromethane

Conditions de réaction

Traitement

1. 1
   Températurecooled to -78° C
2. 2
   workup.STIRRINGThe mixture was stirred for 30 minutes at -78° C.
3. 3
   Températureto warm to -50° C. over 30 minutes
4. 4
   AutreThe cooling bath was removed
5. 5
   workup.STIRRINGthe reaction mixture was stirred at room temperature for 2 hours
6. 6
   TempératureThe mixture was then cooled to 5° C.
7. 7
   workup.ADDITIONhydrogen peroxide (11.5 ml, 30% w/v aqueous solution) was added
8. 8
   workup.STIRRINGThe mixture was stirred for 30 minutes
9. 9
   workup.ADDITIONpoured into water (50 ml)
10. 10
    Extractionextracted with dichloromethane (3×100 ml)
11. 11
    SéchageThe combined extracts were dried (MgSO4)
12. 12
    Autreevaporated
13. 13
    AutreThe residue was purified by flash column chromatography
14. 14
    Lavageeluting with ethyl acetate/hexane (1:1 v/v
15. 15
    Températuregradually increasing to 100% ethyl acetate),

Mode opératoire

A 1M solution of dibutylboron triflate in dichloromethane (32.7 ml) was added to a solution of A (6.28 g) in dry dichloromethane (110 ml), cooled to 5° C. under argon, followed by diisopropylethylamine (6.25 ml). The reaction mixture was stirred at 5° C. for 30 minutes and then cooled to -78° C. 3-Pyridinecarboxaldehyde (3.1 ml) was added dropwise. The mixture was stirred for 30 minutes at -78° C., and then allowed to warm to -50° C. over 30 minutes. The cooling bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The mixture was then cooled to 5° C. and hydrogen peroxide (11.5 ml, 30% w/v aqueous solution) was added. The mixture was stirred for 30 minutes and then poured into water (50 ml) and extracted with dichloromethane (3×100 ml). The combined extracts were dried (MgSO4) and evaporated. The residue was purified by flash column chromatography, eluting with ethyl acetate/hexane (1:1 v/v, gradually increasing to 100% ethyl acetate), to give (4S)-(3-[(2S)-2-[(1S-1-hydroxy-1-(3-pyridyl)methyl]pent-4-enoyl)-4-isopropyloxazolidin-2-one (B), as a solid, m.p. 112°-113° C. (after recrystallisation from toluene); 25 [α]D =+136.0 (EtOH, c 0.311); NMR: 0.85(6H,dd,J=7 Hz), 2.15-2.7(4H,m), 4.0-4.2(2H,m), 4.3-4.55(2H,m), 4.95-5.1(3H,m), 5.65-5.9(1H,m), 7.25-7.35(1H,m), 7.75-7.85(1H,m), 8.5-8.65(2H,m).

Source