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

온도

0 °C

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%).

1. additionwas then added
2. customto give a precipitate
3. filtrationbefore filtering through celite into a flask at 0° C
4. washThe pad was washed with precooled ethyl acetate
5. washThe combined filtrate and wash
6. waitthe reaction left at 0° C. for 3 h
7. temperaturebefore warming to room temperature
8. customExcess diazomethane was removed
9. customby bubbling nitrogen through the solution which
10. concentrationwas then concentrated
11. customto give a yellow gum
12. stirringthen stirred for 2.5 h at room temperature
13. concentrationThe black solution was concentrated under reduced pressure
14. washthen 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. dry with materialThe dried (MgSO4) organic phase
16. customwas evaporated
17. customto leave a yellow oil which
18. customwas purified by column chromatography on flash silica eluting with a gradient of 15-50% ethyl acetate in cyclohexane

ORD 기록

ord-c51094382a6941e79dbde39a000c486b

출처 데이터셋

uspto-grants-1999_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05889178