反应详情

A 200 ml capacity flask was charged with 5.00 g of (3S)-3-hydroxy-N-methyl-3-(2-thienyl)propionamide (optical purity >99.5% ee) and 26 ml of toluene. A 18.3 g portion of 75% by weight toluene solution of sodium bis(2-methoxyethoxy)aluminum hydride was adjusted to 50% by weight by diluting with toluene and added dropwise to the reaction solution at 50° C. spending 10 minutes and stirred for 2 hours. The reaction solution was cooled down to room temperature and mixed with 30 ml of 11% sodium hydroxide aqueous solution, and then the organic layer and water layer were separated. The water layer was extracted twice with 10 ml of toluene, the organic layers were combined, and then 404 mg of L-(+)-tartaric acid and 10 ml of saturated brine were added thereto and stirred for 20 minutes. The mixed solution was separated between layers and then the organic layer was concentrated to obtain 4.27 g of a brown oily substance. When the amount of aluminum contained in this oily substance was measured by the ICP-AES determination method, it was 5 ppm or less. This oily substance was dissolved in 30 ml of toluene, mixed with 0.3 g of activated carbon and stirred for 30 minutes, and then the activated carbon was removed by filtration. The solution was concentrated, mixed with 7 ml of toluene and stirred at room temperature, and then the thus formed pale yellow crystals were collected by filtration, washed with 4 ml of toluene and dried under a reduced pressure to obtain 1.88 g of (1S)-3-methylamino-1-(2-thienyl)-1-propanol (yield 41%).

1. additionadded dropwise to the reaction solution at 50° C.
2. customthe organic layer and water layer were separated
3. extractionThe water layer was extracted twice with 10 ml of toluene
4. addition404 mg of L-(+)-tartaric acid and 10 ml of saturated brine were added
5. stirringstirred for 20 minutes
6. customThe mixed solution was separated between layers
7. concentrationthe organic layer was concentrated
8. customto obtain 4.27 g of a brown oily substance
9. additionmixed with 0.3 g of activated carbon
10. stirringstirred for 30 minutes
11. customthe activated carbon was removed by filtration
12. concentrationThe solution was concentrated
13. additionmixed with 7 ml of toluene
14. stirringstirred at room temperature
15. filtrationthe thus formed pale yellow crystals were collected by filtration
16. washwashed with 4 ml of toluene
17. customdried under a reduced pressure