Reaction #48707

ord-50f5559b755c41c4bb23b87a638117e2

Reaction equation

CC(=O)N[C@@H](Cc1cccc(O)c1)[C@H](O)[C@H]1CO[C@@H](OCC2(C)CCCC2)CN1C(=O)OC(C)(C)C
(2R,5R)-5-[(1S,2S)-2-acetylamino-1-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(1-methylcyclopentylmethoxy)-morpholine-4-carboxylic acid tert-butyl ester
FC(F)CBr
2,2-difluoro-1-bromoethane
O=C([O-])[O-].[Cs+].[Cs+]
cesium carbonate
→
CC(=O)N[C@@H](Cc1cccc(OCC(F)F)c1)[C@H](O)[C@H]1CO[C@@H](OCC2(C)CCCC2)CN1C(=O)OC(C)(C)C
desired compound
CC(=O)N[C@@H](Cc1cccc(OCC(F)F)c1)[C@H](O)[C@H]1CO[C@@H](OCC2(C)CCCC2)CN1C(=O)OC(C)(C)C
(2R,5R)-5-{(1S,2S)-2-Acetylamino-3-[3-(2,2-difluoroethoxy)-phenyl]-1-hydroxypropyl}-2-(1-methylcyclopentylmethoxy)-morpholine-4-carboxylic acid tert-butyl ester

Reactants

CC(=O)N[C@@H](Cc1cccc(O)c1)[C@H](O)[C@H]1CO[C@@H](OCC2(C)CCCC2)CN1C(=O)OC(C)(C)C
(2R,5R)-5-[(1S,2S)-2-acetylamino-1-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(1-methylcyclopentylmethoxy)-morpholine-4-carboxylic acid tert-butyl ester
FC(F)CBr
2,2-difluoro-1-bromoethane
O=C([O-])[O-].[Cs+].[Cs+]
cesium carbonate

Reagents

None

Solvents

CN(C)C=O
N,N-dimethylformamide
CCOC(C)=O
ethyl acetate

Conditions

Temperature
60°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Washwash with saturated aqueous sodium chloride
  2. 2
    Otherdry
  3. 3
    Otherpurify
  4. 4
    Wash(silica gel chromatography, eluting with 1:1 ethyl acetate:dichloromethane)

Procedure

Dissolve (2R,5R)-5-[(1S,2S)-2-acetylamino-1-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(1-methylcyclopentylmethoxy)-morpholine-4-carboxylic acid tert-butyl ester (204 mg) and 2,2-difluoro-1-bromoethane (0.065 mL) and cesium carbonate (391 mg) in N,N-dimethylformamide (5 mL) and heat to 60° C. for 18 hours. Dilute with ethyl acetate, wash with saturated aqueous sodium chloride, dry and purify (silica gel chromatography, eluting with 1:1 ethyl acetate:dichloromethane), to give the desired compound (223 mg).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07745438B2uspto-grants-2010_06