Hydrochloric Acid → HCID 86687330, compound

Temperature

0 °C

A solution of (1S,4R)—N-benzyl-2-hydroxyimino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (IXa) (45.0 g, 134 mmol) in ethanol (360 mL) was added dropwise to a solution of sodium acetate (94.5 g, 1150 mmol) and TiCl3 (460 mmol) in 10.5% wt. aq. HCl (320 mL) at −20 to −10° C. The addition was conducted below 0° C., and the reaction mixture was then stirred at 0° C. for an hour prior to addition of neat t-BuNH2.BH3 (29.1 g, 335 mmol) in portions. The mixture was stirred at 0-10° C. for 30 minutes and then at ambient temperature. After the reaction was completed, the solution was diluted with ethyl acetate (675 mL) and was extracted with water (450 mL). Following separation of the layers, the organic layer was washed with sat. aq. NH4Cl (675 mL), 1 M aq. Na2CO3 (900 mL) and finally with 10% aq. NaCl (450 mL). The organic solution was concentrated to give the crude amine product (1S,2R,4R)—N-benzyl-2-amino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (VIa) as light yellow powder. The crude product was dissolved in ethanol (180 mL) at 70-75° C. and was hot-filtered. The filter cake was washed with hot ethanol (45 mL), and the filtrate was slowly cooled allowing recrystallization to occur at about 50° C. After stirring for an hour at 0° C., the white suspension was filtered and washed with cold ethanol (45 mL) to give pure (1S,2R,4R)—N-benzyl-2-amino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (VIa) as a white powder (23.5 g; 54%; >99.9% pure as assessed by HPLC).

1. additionThe addition
2. customwas conducted below 0° C.
3. stirringThe mixture was stirred at 0-10° C. for 30 minutes
4. customat ambient temperature
5. extractionwas extracted with water (450 mL)
6. customseparation of the layers
7. washthe organic layer was washed with sat. aq. NH4Cl (675 mL), 1 M aq. Na2CO3 (900 mL) and finally with 10% aq. NaCl (450 mL)
8. concentrationThe organic solution was concentrated
9. customto give the crude amine product (1S,2R,4R)—N-benzyl-2-amino-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonamide (VIa) as light yellow powder
10. filtrationwas hot-filtered
11. washThe filter cake was washed with hot ethanol (45 mL)
12. temperaturethe filtrate was slowly cooled
13. customrecrystallization
14. customto occur at about 50° C
15. stirringAfter stirring for an hour at 0° C.
16. filtrationthe white suspension was filtered
17. washwashed with cold ethanol (45 mL)

ORD record

ord-3ee27bdc72c8477a817fbf80c5ab743b

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859765B2