反应详情

The process is performed as in Example 3, starting with 0.7 g of diastereoisomer B of N-(tert-butyl)-N′-((1S)-1-benzyl-2-hydroxypropyl)thiourea which is heated to a temperature in the region of 100° C. for 5 hours in 8.3 cm3 of aqueous 6N hydrochloric acid. After concentration of the reaction medium under reduced pressure (5 kPa) at a temperature in the region of 50° C., 50 cm3 of water are added to the residue obtained and the solution is then extracted with 3 times 25 cm3 of dichloromethane. The aqueous phase is made alkaline by addition of 0.5 cm3 of 30% caustic soda and extracted with 3 times 50 cm3 of dichloromethane. The extracts are combined, dried over sodium sulfate, filtered and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 50° C. An oil is obtained, which is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-63μ; diameter 2 cm; height 28 cm), eluting with a dichloromethane/methanol mixture (95/5 by volume). The fractions containing the expected product are collected. These fractions are combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.10 g of (4S)-4-benzyl-5-methyl-4,5-dihydro-1,3-thiazol-2-ylamine is obtained in the form of a pale pink solid melting at 90° C. to become pasty (mixture of diastereoisomers: 82% of cis [(4S,5R)-4-benzyl-5-methyl-4,5-dihydro-1,3-thiazol-2-ylamine] 18% of trans [(4S,5S)-4-benzyl-5-methyl-4,5-dihydro-1,3-thiazol-2-ylamine]). (Rf=0.15 in a 95/5 by volume mixture of dichloromethane/methanol, on a Merck 60F254R silica plate).

1. customobtained
2. extractionthe solution is then extracted with 3 times 25 cm3 of dichloromethane
3. additionby addition of 0.5 cm3 of 30% caustic soda
4. extractionextracted with 3 times 50 cm3 of dichloromethane
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 50° C
8. customAn oil is obtained
9. customwhich is purified by chromatography under an argon pressure of 50 kPa
10. washon a column of silica gel (particle size 40-63μ; diameter 2 cm; height 28 cm), eluting with a dichloromethane/methanol mixture (95/5 by volume)
11. additionThe fractions containing the expected product
12. customare collected
13. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C