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

HRID 513106Notes

Reaction equation

HRID 513106 reaction equation
C[Si](C)(C)CC[O:5][CH2:6][C:7]1([C:20]([O:22][CH3:23])=[O:21])[O:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]1.C(O)(C(F)(F)F)=O.C(N(C(C)C)C(C)C)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C(Cl)Cl.O>[OH:5][CH2:6][C:7]1([C:20]([O:22][CH3:23])=[O:21])[O:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH2:8]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 68354670HCID 68354670, compound

Product 1

HCID 672284574-Tert-butyl 2-methyl 2-(hydroxymethyl)morpholine-2,4-dicarboxylateYield 72.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-cd43b3d2a6c9480b875d5daf9e628af7
Source dataset
uspto-grants-2015_08
Patent number
US09102676B2

Reaction notes

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