Methyl iodide → tert-butyl N-[(2S)-2-methoxypropyl]carbamate

Cool a solution of tert-butyl [(2S)-2-hydroxypropyl]carbamate (870 g, 4.96 mol) in tetrahydrofuran (10 L) to 5° C. Add sodium hydride (60% dispersion, 248 g, 6.21 mol, 1.25 eq.) in portions over 8 minutes. Stir the reaction at 5° C. for 30 minutes. Add methyl iodide (387 mL, 6.21 mol, 1.25 eq.) dropwise over 5 minutes and allow the reaction to proceed at 5-10° C. for 45 minutes. Quench the reaction with water (1 L) and extract with ethyl acetate (4 L). Obtain the organic layer and concentrate it in vacuo to obtain a residue. Co-evaporate the residue with toluene (2×1 L), dilute with dichloromethane (2 L) and filter. Rinse remaining solid with additional dichloromethane (500 mL). Concentrate the combined dichloromethane liquid filtrate in vacuo to obtain a crude intermediate of tert-butyl N-[(2S)-2-methoxypropyl]carbamate (880 g, 94%).

1. customthe reaction at 5° C. for 30 minutes
2. customthe reaction
3. customQuench
4. customthe reaction with water (1 L)
5. extractionextract with ethyl acetate (4 L)
6. customObtain the organic layer
7. concentrationconcentrate it in vacuo
8. customto obtain a residue
9. customCo-evaporate the residue with toluene (2×1 L)
10. additiondilute with dichloromethane (2 L)
11. filtrationfilter
12. washRinse
13. concentrationConcentrate the combined dichloromethane liquid filtrate in vacuo

ORD record

ord-18c71c74718a41e1a2a336aeea564e21

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658668B2