Reaktion #430609

Reaktionsgleichung

9-amino-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane

(S)-4-amino-5-chloro-2-[(1-methyl-2-butynyl)oxy]benzoic acid

triethylamine

sodium hydroxide

9-amino-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane

ethyl chloroformate

→

title compound

3,7-Dimethyl-3,7-diazabicyclo[3.3.1]non-9-yl-4-amino-5-chloro-2-(1-methyl-2-butynyl)oxybenzamide

Lösungsmittel

water

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONfollowed by the addition
2. 2
   Sonstigewas brought to room temperature
3. 3
   workup.STIRRINGThe obtained mixture was stirred for 30 minutes
4. 4
   workup.ADDITIONfollowed by the addition
5. 5
   Sonstigeat room temperature
6. 6
   workup.STIRRINGThe obtained mixture was stirred for one hour
7. 7
   workup.ADDITIONfollowed by the addition
8. 8
   SonstigeThe organic phase was recovered
9. 9
   Trocknendried over anhydrous magnesium sulfate
10. 10
    Einengenconcentrated in a vacuum
11. 11
    SonstigeThe residue was purified by silica gel column chromatography (with 0 to 10 to 20% methanol/chloroform

Vorschrift

A solution of 546 mg of (S)-4-amino-5-chloro-2-[(1-methyl-2-butynyl)oxy]benzoic acid and 0.9 ml of triethylamine in 10 ml of dichloromethane was cooled with ice, followed by the addition thereto of 0.225 ml of ethyl chloroformate. The obtained mixture was stirred for 10 minutes, while the temperature was brought to room temperature. 400 mg of 9-amino-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane was added to the resulting mixture at room temperature. The obtained mixture was stirred for 30 minutes, followed by the addition thereto of 200 mg of 9-amino-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane at room temperature. The obtained mixture was stirred for one hour, followed by the addition thereto of dichloromethane and water. The pH of the aqueous layer was adjusted to 10 or above with a 2.5N aqueous solution of sodium hydroxide. The organic phase was recovered, dried over anhydrous magnesium sulfate, and concentrated in a vacuum. The residue was purified by silica gel column chromatography (with 0 to 10 to 20% methanol/chloroform and then with chloroform/methanol/aqueous ammonia (75/25/1.5) to give 650 mg of the title compound.

Quelle