Reaktion #71264

Reaktionsgleichung

((1R,4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonic acid

5-bromo-2,3-dihydro-1H-inden-2-amine hydrobromide

N-methylmorpholine

→

fluffy white solid

Ausbeute 37.9%

(S)-5-bromo-2,3-dihydro-1H-inden-2-amine((1R,4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate

Ausbeute 37.9%

Lösungsmittel

methanol

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturmaintaining internal temp at 60-65° C
2. 2
   WaschenThe addition funnel was rinsed with MeOH (13.3 mL) and rinsings
3. 3
   workup.ADDITIONadded to reaction
4. 4
   Sonstigewas obtained
5. 5
   Temperaturto cool to room temperature
6. 6
   workup.STIRRINGstirred for a total of 4 h
7. 7
   FiltrationThe solids were collected by filtration
8. 8
   Waschenwashed with a pre-cooled mixture of isopropyl acetate/methanol 2:1 (2×15 mL)
9. 9
   TrocknenThe crude product was dried in a vacuum oven at 50° C. overnight

Vorschrift

To a suspension of 5-bromo-2,3-dihydro-1H-inden-2-amine hydrobromide (107 mmol, 31.27 g) and N-methylmorpholine (112 mmol, 12.32 mL, 11.33 g) in methanol (66.6 mL) was heated to 58-62° C. and a solution of ((1R,4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonic acid (107 mmol, 24.79 g) in methanol (53.4 mL) was added over 3 min maintaining internal temp at 60-65° C. The addition funnel was rinsed with MeOH (13.3 mL) and rinsings added to reaction. The mixture was stirred at 60-65° C. for 10 min until a clear solution was obtained. The reaction was then allowed to cool to room temperature and stirred for a total of 4 h. The solids were collected by filtration and washed with a pre-cooled mixture of isopropyl acetate/methanol 2:1 (2×15 mL) followed by water (2×15 mL). The crude product was dried in a vacuum oven at 50° C. overnight to yield (18.03 g) of a fluffy white solid. This was suspended in methanol (130 mL) and heated to reflux for 4 h then allowed to cool to room temperature with stirring over 2 h and stirring continued at room temperature for a further 1 h. Solids were then isolated by filtration and washed with a pre-cooled solution of isopropylacetate/methanol (2:1, 2×18 mL). The colourless solid (13.82 g) was dried in the vacuum oven for 60 h. Refluxing in methanol followed by washing the solid with isopropyl acetate/methanol was repeated until the desired enantiomeric ratio was obtained. (S)-5-bromo-2,3-dihydro-1H-inden-2-amine((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate was obtained as a colourless solid (12.28 g, e.e. 100:0, 25.9%).

Quelle