Reacción #1507483

Ecuación de reacción

triethylamine

4-Methylmorpholine

t-butoxycarbonyl-L-glutamic acid 5-benzyl ester

i-Butyl chloroformate

diazomethane

ether

→

title compound

Rendimiento 27.0%

(S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino]-hexanedioic acid 1-methyl 6-(phenylmethyl) ester

Rendimiento 27.0%

Disolventes

methanol

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas then added
2. 2
   Otroto give a precipitate
3. 3
   Filtraciónbefore filtering through celite into a flask at 0° C
4. 4
   LavadoThe pad was washed with precooled ethyl acetate
5. 5
   LavadoThe combined filtrate and wash
6. 6
   workup.WAITthe reaction left at 0° C. for 3 h
7. 7
   Temperaturabefore warming to room temperature
8. 8
   OtroExcess diazomethane was removed
9. 9
   Otroby bubbling nitrogen through the solution which
10. 10
    Concentraciónwas then concentrated
11. 11
    Otroto give a yellow gum
12. 12
    workup.STIRRINGthen stirred for 2.5 h at room temperature
13. 13
    ConcentraciónThe black solution was concentrated under reduced pressure
14. 14
    Lavadothen washed with saturated aqueous sodium bicarbonate solution (100 ml), water (100 ml), 1M aqueous potassium hydrogen sulphate solution (2×100 ml) and brine (100 ml)
15. 15
    SecadoThe dried (MgSO4) organic phase
16. 16
    Otrowas evaporated
17. 17
    Otroto leave a yellow oil which
18. 18
    Otrowas purified by column chromatography on flash silica eluting with a gradient of 15-50% ethyl acetate in cyclohexane

Procedimiento

4-Methylmorpholine (2 ml) was added to a solution of t-butoxycarbonyl-L-glutamic acid 5-benzyl ester (6.75 g, 20 mmol) in ethyl acetate (60 ml) at 0° C. i-Butyl chloroformate (2.61 ml, 20 mmol) was then added to give a precipitate and the mixture was stirred for 15 min at 0° C. before filtering through celite into a flask at 0° C. The pad was washed with precooled ethyl acetate. The combined filtrate and wash was treated with diazomethane in ether (30 mmol in 100 ml) over 5 min and the reaction left at 0° C. for 3 h before warming to room temperature. Excess diazomethane was removed by bubbling nitrogen through the solution which was then concentrated to give a yellow gum. The gum was dissolved in methanol (100 ml), treated with silver benzoate (1 g, 4.4 mmol) and triethylamine (10 ml, 70 mmol) then stirred for 2.5 h at room temperature. The black solution was concentrated under reduced pressure and the residue taken up in ethyl acetate (100 ml) then washed with saturated aqueous sodium bicarbonate solution (100 ml), water (100 ml), 1M aqueous potassium hydrogen sulphate solution (2×100 ml) and brine (100 ml). The dried (MgSO4) organic phase was evaporated to leave a yellow oil which was purified by column chromatography on flash silica eluting with a gradient of 15-50% ethyl acetate in cyclohexane to give the title compound (1.972 g) as a white solid which crystallised from cyclohexane m.p.60°-61° C., [α]D -21° (CHCl3 c=1%).

Fuente