Dimethylformamide → HCID 71264777, compound

To a 0° C. solution of R-5 (15 mmol, 3.0 g) in THF (50 mL) is added methylmagnesium chloride (1.5M in THF, 18 mmol, 12 mL). The solution is stirred for 5 min then treated with a solution of n-BuLi (2.6M in hexanes, 45 mmol, 18 mL). The solution is stirred for 5 min then treated with DMF (150 mmol, 11.0 g). The cold bath is removed and the mixture is stirred for 10 min then treated with water, extracted with CH2Cl2 and filtered through a phase separator. The filtrate is concentrated in vacuo to give R-7 (2.20 g, 99%). To a solution of R-7 (14.5 mmol, 2.20 g) and morpholine (44 mmol, 38.00 g) in DCE (dichloroethane) (150 mL) is added sodium triacetoxyborohydride (73 mmol, 15.50 g). The mixture is stirred at 60° C. for 24 h then cooled to ambient temperature and poured into 20% (w/w) aqueous Na2CO3 and extracted with 10% methanol in CH2Cl2. The organics are collected, dried over MgSO4, filtered, and concentrated in vacuo. The residue is purified by flash chromatography to give the title intermediate (2.50 g, 76%).

1. stirringThe solution is stirred for 5 min
2. customThe cold bath is removed
3. stirringthe mixture is stirred for 10 min
4. additionthen treated with water
5. extractionextracted with CH2Cl2
6. filtrationfiltered through a phase separator
7. concentrationThe filtrate is concentrated in vacuo
8. customto give R-7 (2.20 g, 99%)
9. stirringThe mixture is stirred at 60° C. for 24 h
10. extractionextracted with 10% methanol in CH2Cl2
11. customThe organics are collected
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe residue is purified by flash chromatography

ORD record

ord-0bfe5b4ccbc341d188bb31289c498b6a

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815857B2