反应详情

温度

60 °C

A suspension of 7-(2-amino-ethyl)-4-hydroxy-3H-benzothiazol-2-one hydrochloride (53 g) in dry NMP (216 mL) was heated to 60° C. and treated in one portion with a solution of NaOH (8.2 g) in methanol (102 mL). The bright orange suspension was cooled to room temperature and treated dropwise with a solution of N-[2-(diethylamino)ethyl]-3-[2-(1-naphthyl)ethoxy]-N-(2-oxoethyl)propanamide in dichloromethane (475 mL) over 20 minutes. The reaction was left to stir for 25 minutes. Sodium triacetoxyborohydride (91.5 g) was then added in portions over 20 minutes and the mixture stirred for a further 50 minutes. The reaction mixture was poured into water (1.8 L) and the acidic solution (pH5) was washed with tert. butyl methyl ether (TBME) (3×500 mL). The aqueous phase was basified to pH8 by the addition of solid potassium carbonate and extracted with dichloromethane (3×750 mL); the combined organic extracts were dried over magnesium sulphate and concentrated to give a dark oil. This was dissolved in ethanol (200 mL) and 48% aqueous hydrobromic acid (73 mL) was added. The solution was aged for 30 minutes then evaporated to dryness. The residue was triturated with ethanol (560 mL); the resultant solid was collected by filtration and dried in vacuo at 50° C. The sticky solid was suspended in boiling ethanol (100 mL) and filtered while hot. The collected solid was dried in vacuo at 50° C. This material was recrystallised from ethanol/water (3:1, 500 mL). After standing overnight the resultant solid was collected by filtration and washed with ice-cold ethanol (75 mL). Drying in vacuo at 50° C. for 24 hr afforded 57 g of the title compound.

1. temperatureThe bright orange suspension was cooled to room temperature
2. waitThe reaction was left
3. stirringthe mixture stirred for a further 50 minutes
4. washthe acidic solution (pH5) was washed with tert. butyl methyl ether (TBME) (3×500 mL)
5. additionThe aqueous phase was basified to pH8 by the addition of solid potassium carbonate
6. extractionextracted with dichloromethane (3×750 mL)
7. dry with materialthe combined organic extracts were dried over magnesium sulphate
8. concentrationconcentrated
9. customto give a dark oil
10. waitThe solution was aged for 30 minutes
11. customthen evaporated to dryness
12. customThe residue was triturated with ethanol (560 mL)
13. filtrationthe resultant solid was collected by filtration
14. customdried in vacuo at 50° C
15. filtrationfiltered while hot
16. customThe collected solid was dried in vacuo at 50° C
17. customThis material was recrystallised from ethanol/water (3:1, 500 mL)
18. waitAfter standing overnight
19. filtrationthe resultant solid was collected by filtration
20. washwashed with ice-cold ethanol (75 mL)
21. customDrying in vacuo at 50° C. for 24 hr