Carbon tetrabromide → tert-Butyl 2-(bromomethyl)morpholine-4-carboxylate

To a cooled (0° C.) solution of 2-hydroxymethylmorpholine-4-carboxylic acid tert-butyl ester (1.04 g, 4.79 mmol, see Step 1) in dichloromethane (20 mL) was added CBr4 (1.98 g, 5.98 mmol). After stirring the mixture for 10 minutes, triphenylphosphine (2.20 g, 8.38 mmol) was added portion-wise. The reaction mixture was stirred at 0° C. for 6 hours and then allowed to warm to room temperature and stirred for 60 hours. The mixture was concentrated under reduced pressure and then diluted with ether. The crude mixture was filtered and the filtrate was concentrated to afford the crude product, which was chromatographed on Biotage eluting with dichloromethane. The desired fractions were combined and concentrated to yield 0.50 g of product (37% yield).

1. stirringThe reaction mixture was stirred at 0° C. for 6 hours
2. stirringstirred for 60 hours
3. concentrationThe mixture was concentrated under reduced pressure
4. additiondiluted with ether
5. filtrationThe crude mixture was filtered
6. concentrationthe filtrate was concentrated
7. customto afford the crude product, which
8. customwas chromatographed on Biotage
9. washeluting with dichloromethane
10. concentrationconcentrated

ORD record

ord-917b7363b5834323b1315be67f59e3b4

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08518983B2