Trifluoroacetic acid → 4-Tert-butyl 2-methyl 2-(hydroxymethyl)morpholine-2,4-dicarboxylate

E2 (6.09 g, 16.22 mmol) was dissolved in DCM (100 mL), TFA (26.5 mL, 357 mmol) was added and the solution was stirred for 3 days at RT. The reaction mixture was concentrated and the residue was dissolved in DCM (100 mL). N-ethyl-N-isopropylpropan-2-amine (15 mL, 86 mmol) and di-tert-butyl dicarbonate (10.62 g, 48.7 mmol,) were added and the solution was stirred for 2 h at RT. Water was added and the mixture was extracted twice with DCM. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography from toluene:acetone 100:0 to 50:50 which gave the title compound (3.22 g, 72%). 1H NMR (400 MHz, CDCl3, 300K): δ 1.46 (9H, s), 2.24 (1H, m), 3.05 (2H, m), 3.64-4.14 (7H, m), 4.32 (1H, d, J=13.7 Hz); MS (ES) C12H21NO6 requires: 275. found: 298.2 [M+Na]+.

1. concentrationThe reaction mixture was concentrated
2. dissolutionthe residue was dissolved in DCM (100 mL)
3. stirringthe solution was stirred for 2 h at RT
4. extractionthe mixture was extracted twice with DCM
5. washThe organic layer was washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by flash column chromatography from toluene:acetone 100:0 to 50:50 which

ORD record

ord-cd43b3d2a6c9480b875d5daf9e628af7

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102676B2