Réaction #46049

Équation de réaction

diisopropylethylamine

Methanesulfonyl chloride

diisopropylethylamine

(αS)-α[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid

Formula 3

(αS)-α[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid

(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide hydrochloride salt

hydroxybenzotriazole

→

3-cyano-(αS)-α-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid, 1,1-dimethylethyl ester

Solvants

THF

Conditions de réaction

Traitement

1. 1
   AutreA 2 L three-necked flask equipped with a thermometer, a mechanical stirrer and a gas inlet
2. 2
   Autreto produce a clear solution
3. 3
   Autrethe internal temperature below 8° C
4. 4
   workup.STIRRINGThe reaction mixture was stirred at 0° C. until all acid
5. 5
   Autrethe flask was removed from the cooling bath
6. 6
   workup.STIRRINGThe reaction mixture was stirred at room temperature for 2 hours

Mode opératoire

A 2 L three-necked flask equipped with a thermometer, a mechanical stirrer and a gas inlet was charged with (αS)-α[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid (Formula 3) (50 grams, 153.8 mmol). THF (200 ml) was added and stirred to produce a clear solution. The solution was cooled to −6° C. in an acetone-dry ice-water bath. Methanesulfonyl chloride (Mes-Cl) (13.1 ml, 169 mmol, 1.1 equivalents) was then added as a single portion followed by diisopropylethylamine (94 ml, 539 mmol, 1.1 equivalents). The diisopropylethylamine was added slowly over a period of about 4 minutes to keep the internal temperature below 8° C. The reaction mixture was stirred at 0° C. until all acid was converted to mixed anhydride. (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide hydrochloride salt (32.5 grams, 200 mmol, 1.1 equivalents) and hydroxybenzotriazole (HOBT) (1.04 grams, 7.6 mmol, 0.05 equivalents) were then added in a single portion and the flask was removed from the cooling bath. The reaction mixture was stirred at room temperature for 2 hours and then left overnight at room temperature.

Source