Reaction #48723

ord-ca9cb4295a3b413c9a13f3b4c63cfdb0

Reaction equation

CC(C)CBr
1-bromo-2-methyl-propane
CC(=O)N[C@@H](Cc1cc(O)cc(F)c1)[C@H](O)[C@H]1CO[C@@H](OCC(C)(C)C)[C@H](C)N1C(=O)OC(C)(C)C
(2R,3S,5R)-5-[(1S,2S)-2-acetylamino-3-(3-fluoro-5-hydroxy-phenyl)-1-hydroxy-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid tert-butyl ester
O=C([O-])[O-].[Cs+].[Cs+]
cesium carbonate
→
CC(=O)N[C@@H](Cc1cc(F)cc(OCC(C)C)c1)[C@H](O)[C@H]1CO[C@@H](OCC(C)(C)C)[C@H](C)N1C(=O)OC(C)(C)C
title compound
Yield 55.0%
CC(=O)N[C@@H](Cc1cc(F)cc(OCC(C)C)c1)[C@H](O)[C@H]1CO[C@@H](OCC(C)(C)C)[C@H](C)N1C(=O)OC(C)(C)C
(2R,3S,5R)-5-[(1S,2S)-2-Acetylamino-3-(3-fluoro-5-isobutoxy-phenyl)-1-hydroxypropyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid tert-butyl ester
Yield 55.0%

Reactants

CC(C)CBr
1-bromo-2-methyl-propane
CC(=O)N[C@@H](Cc1cc(O)cc(F)c1)[C@H](O)[C@H]1CO[C@@H](OCC(C)(C)C)[C@H](C)N1C(=O)OC(C)(C)C
(2R,3S,5R)-5-[(1S,2S)-2-acetylamino-3-(3-fluoro-5-hydroxy-phenyl)-1-hydroxy-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid tert-butyl ester
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
    TemperatureCool to room temperature
  2. 2
    WashWash (0.1N citric acid, 10% potassium carbonate, saturated aqueous sodium chloride)
  3. 3
    Dryingdry (magnesium sulfate)
  4. 4
    Filtrationfilter
  5. 5
    Concentrationconcentrate
  6. 6
    OtherPurify on 12 g silica gel column
  7. 7
    Washeluting with 100:0 to 40:60 hexanes

Procedure

Add 1-bromo-2-methyl-propane (0.05 g, 0.35 mmol) to (2R,3S,5R)-5-[(1S,2S)-2-acetylamino-3-(3-fluoro-5-hydroxy-phenyl)-1-hydroxy-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid tert-butyl ester (0.12 g, 0.23 mmol) and cesium carbonate (0.15 g, 0.46 mmol) in N,N-dimethylformamide (3 mL) under nitrogen and heat in a 60° C. oil bath for 2.5 hours. Cool to room temperature and dilute with ethyl acetate. Wash (0.1N citric acid, 10% potassium carbonate, saturated aqueous sodium chloride), dry (magnesium sulfate), filter and concentrate. Purify on 12 g silica gel column eluting with 100:0 to 40:60 hexanes:ethyl acetate to give 0.072 g (54.5%) of the title compound as a white foam.

Source

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