Réaction #48631

ord-09d161281e8047b8a1ed6073750586a1

Équation de réaction

CCCCBr
1-bromobutane
CC(=O)N[C@@H](Cc1cccc(O)c1)[C@H](O)C1CO[C@@H](OCC(C)(C)C)[C@H](C)N1C(=O)OC(C)(C)C
5-[2-(S)-acetylamino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(R)-(2,2-dimethylpropoxy)-3-(S)-methylmorpholine-4-carboxylic acid tert-butyl ester
O=C([O-])[O-].[Cs+].[Cs+]
cesium carbonate
→
CCCCOc1cccc(C[C@H](NC(C)=O)[C@H](O)[C@H]2CO[C@@H](OCC(C)(C)C)[C@H](C)N2C(=O)OC(C)(C)C)c1
title compound
Rendement 102.5%
CCCCOc1cccc(C[C@H](NC(C)=O)[C@H](O)[C@H]2CO[C@@H](OCC(C)(C)C)[C@H](C)N2C(=O)OC(C)(C)C)c1
5-(R)-[2-(S)-Acetylamino-3-(3-butoxyphenyl)-1-(S)-hydroxypropyl]-2-(R)-(2,2-dimethylpropoxy)-3-(S)-methylmorpholine-4-carboxylic acid tert-butyl ester
Rendement 102.5%

Réactifs

CCCCBr
1-bromobutane
CC(=O)N[C@@H](Cc1cccc(O)c1)[C@H](O)C1CO[C@@H](OCC(C)(C)C)[C@H](C)N1C(=O)OC(C)(C)C
5-[2-(S)-acetylamino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(R)-(2,2-dimethylpropoxy)-3-(S)-methylmorpholine-4-carboxylic acid tert-butyl ester
O=C([O-])[O-].[Cs+].[Cs+]
cesium carbonate

Réactifs

Aucun

Solvants

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

Conditions de réaction

Température
60°CELSIUS
Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    Lavagewash with water
  2. 2
    Séchagedry (magnesium sulfate)
  3. 3
    Filtrationfilter
  4. 4
    Concentrationconcentrate
  5. 5
    Autrepurify
  6. 6
    Lavage(silica gel chromatography, eluting with 20:80 to 85:15 ethyl acetate:dichloromethane)

Mode opératoire

Add 1-bromobutane (6 μL, 55.6 μmol) to a solution of 5-[2-(S)-acetylamino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(R)-(2,2-dimethylpropoxy)-3-(S)-methylmorpholine-4-carboxylic acid tert-butyl ester (25 mg, 50.5 μmol) and cesium carbonate (33 mg, 1.01 mmol) in N,N-dimethylformamide (250 μL). Heat to 60° C. for 3 hours. Dilute with ethyl acetate, wash with water, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 20:80 to 85:15 ethyl acetate:dichloromethane) to give the title compound (28.5 mg, 80%).

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US07745438B2uspto-grants-2010_06