Reaktion #48686

Reaktionsgleichung

tetrabutylammonium fluoride

(2R,5R)-2-(2,2-dimethylpropoxy)-5-formylmorpholine-4-carboxylic acid tert-butyl ester

1,3-difluoro-5-(2-nitroethyl)-benzene

→

desired compound

Ausbeute 34.0%

(2R,5R)-5-[(1R,2S)-3-(3,5-Difluorophenyl)-1-hydroxy-2-nitropropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

Ausbeute 34.0%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONPour into ice cold saturated aqueous sodium chloride
2. 2
   Extraktionextract with ethyl acetate
3. 3
   WaschenWash with 0.1 N aqueous citric acid and saturated aqueous sodium chloride
4. 4
   Trocknendry (magnesium sulfate)
5. 5
   Filtrationfilter
6. 6
   Einengenconcentrate
7. 7
   Sonstigepurify
8. 8
   Waschen(silica gel chromatography, eluting with 20:80 to 30%:70 diethyl ether:hexanes)
9. 9
   Sonstigeto give
10. 10
    workup.ADDITIONa mixture of 2 diastereomers (3.66 g, 75:25 mixture) which
11. 11
    Sonstigeare separated

Vorschrift

Add tetrabutylammonium fluoride (18.32 mL, 18.32 mmol, 1.0 M in tetrahydrofuran) to (2R,5R)-2-(2,2-dimethylpropoxy)-5-formylmorpholine-4-carboxylic acid tert-butyl ester (5.02 g, 16.66 mmol) and 1,3-difluoro-5-(2-nitroethyl)-benzene (3.43 g, 18.32 mmol) in tetrahydrofuran (28 mL) at −10° C. and stir 20 minutes. Pour into ice cold saturated aqueous sodium chloride and extract with ethyl acetate. Wash with 0.1 N aqueous citric acid and saturated aqueous sodium chloride, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 20:80 to 30%:70 diethyl ether:hexanes) to give a mixture of 2 diastereomers (3.66 g, 75:25 mixture) which are separated using chiral chromatography to give the desired compound (˜2.45 g, 34.0%).

Quelle