Ethanamine, 2,2,2-trifluoro- → tert-Butyl (2R,5R)-2-ethynyl-5-(2,2,2-trifluoroethylaminocarbonyloxymethyl)morpholine-4-carboxylate

HRID 629750Notes

Reaction equation

HRID 629750 reaction equation
[C:1]([C@H:3]1[O:8][CH2:7][C@@H:6]([CH2:9][OH:10])[N:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:4]1)#[CH:2].[C:18](N1C=CN=C1)(N1C=CN=C1)=[O:19].[F:30][C:31]([F:35])([F:34])[CH2:32][NH2:33]>N1C=CC=CC=1>[C:1]([C@H:3]1[O:8][CH2:7][C@H:6]([CH2:9][O:10][C:18]([NH:33][CH2:32][C:31]([F:35])([F:34])[F:30])=[O:19])[N:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:4]1)#[CH:2]

Participants

5

Reactant 3

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 682631,1'-CarbonyldiimidazoleHCID 86726348tert-Butyl (2R,5R)-2-ethynyl-5-(hydroxymethyl)morpholine-4-carboxylate

Product 1

HCID 86726350tert-Butyl (2R,5R)-2-ethynyl-5-(2,2,2-trifluoroethylaminocarbonyloxymethyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of tert-Butyl (2R,5R)-2-ethynyl-5-(hydroxymethyl)morpholine-4-carboxylate (0.51 g, 2.1 mmol) in 6 mL of pyridine was added carbonyldiimidazole (0.45 g, 2.8 mmol). The mixture was stirred at ambient temperature for 3 h. Trifluoroethylamine (4.1 mL, 53 mmol) was added, the vessel was sealed and heated to 50° C. for 24 h. The pyridine was removed in vacuo and the residue was dissolved in EtOAc and washed with water and brine. The EtOAc solution was dried (MgSO4), filtered, and the solvent was removed in vacuo. The residue was chromatographed on a 40 g SiO2 column using a gradient elution of 0-50% EtOAc in hexanes. Fractions containing product were combined and removal of solvents in vacuo gave a solid.

Workup

  1. customthe vessel was sealed
  2. temperatureheated to 50° C. for 24 h
  3. customThe pyridine was removed in vacuo
  4. dissolutionthe residue was dissolved in EtOAc
  5. washwashed with water and brine
  6. dry with materialThe EtOAc solution was dried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo
  9. customThe residue was chromatographed on a 40 g SiO2 column
  10. washa gradient elution of 0-50% EtOAc in hexanes
  11. additionFractions containing product
  12. customremoval of solvents in vacuo
  13. customgave a solid

Sources & evidence

ORD record
ord-c69e28cffb2047cdb8d95e231fa775ee
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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