Water → tert-butyl (2S,3S)-3,4-bis(tert-butyldimethylsilyloxy)-1-hydroxybutan-2-ylcarbamate

A solution of tert-butyl (1R,2S)-2,3-bis(tert-butyldimethylsilyloxy)-1-(thiazol-2-yl)propylcarbamate (6.150 g, 12.2 mmol) in 120 mL MeCN was treated with 4A mol. sieves and was allowed to stir at room temperature for 10 minutes. Methyl trifluoromethylsulfonate (1.62 ml, 14.7 mmol) was added, and the reaction mixture was allowed to stir for an additional 30 minutes. The reaction mixture was then concentrated in vacuo. The crude residue was dissolved in 100 mL MeOH, cooled to 0° C., and treated with NaBH4 (1.39 g, 36.7 mmol). The reaction mixture was allowed to warm to RT and stir for an additional 20 minutes. The reaction mixture was then concentrated, diluted with EtOAc, filtered through celite and again concentrated in vacuo. The residue was dissolved in 100 mL ACN and 20 mL water and was treated with mercury(II)chloride (3.32 g, 12.2 mmol). After stirring for 30 minutes, an additional portion of NaBH4 (1.39 g, 36.7 mmol) was added, and the reaction mixture was allowed to stir for another 30 minutes. The reaction mixture was quenched with saturated NaHCO3 solution and diluted with EtOAc. The crude reaction mixture was then washed with water then brine. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude residue was forced through a short plug of silica eluting with ether. The filtrate was again concentrated in vacuo yielding tert-butyl (2S,3S)-3,4-bis(tert-butyldimethylsilyloxy)-1-hydroxybutan-2-ylcarbamate (5.33 g, 96.9% yield) with minor impurities.

1. stirringto stir for an additional 30 minutes
2. concentrationThe reaction mixture was then concentrated in vacuo
3. dissolutionThe crude residue was dissolved in 100 mL MeOH
4. temperaturecooled to 0° C.
5. temperatureto warm to RT
6. stirringstir for an additional 20 minutes
7. concentrationThe reaction mixture was then concentrated
8. additiondiluted with EtOAc
9. filtrationfiltered through celite
10. concentrationagain concentrated in vacuo
11. dissolutionThe residue was dissolved in 100 mL ACN
12. stirringAfter stirring for 30 minutes
13. stirringto stir for another 30 minutes
14. customThe reaction mixture was quenched with saturated NaHCO3 solution
15. additiondiluted with EtOAc
16. customThe crude reaction mixture
17. washwas then washed with water
18. dry with materialThe organic layer was dried over MgSO4
19. concentrationconcentrated in vacuo
20. concentrationThe filtrate was again concentrated in vacuo

ORD 기록

ord-653ccd8c2c4f41e593bc51b9773d5b03

출처 데이터셋

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08552181B2