N-tert-butyl-N'-[(1R,2S)-1-(4-pyridylmethyl)-2-hydroxybutyl]thiourea → HCID 178463407, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 4.2 g of N-tert-butyl-N′-[(1R,2S)-1-(4-pyridylmethyl)-2-hydroxybutyl]thiourea in 40 cm3 of 6N hydrochloric acid is heated at a temperature in the region of 100° C. for 20 hours. After cooling to room temperature, the reaction mixture is concentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C. The residue is chromatographed at atmospheric pressure on a column of silica gel (particle size 40-63μ; diameter 3.6 cm; height 24 cm), eluting with a dichloromethane/methanol mixture (98/2 by volume) and then with a dichloromethane/methanol mixture (97/3 by volume). The fractions containing the expected product are combined and then concentrated under the above conditions, taken up in 30 cm3 of dichloromethane and basified with 1N sodium hydroxide. The organic phase is dried over magnesium sulphate, filtered and dried in a desiccator under reduced pressure (0.1 kPa) at a temperature in the region of 40° C. 1.4 g of (+)-(4R,5R)-5-(ethyl-4-(4-pyridylmethyl)-4,5-dihydro-2-thiazolylamine are obtained in the form of a white solid melting at 124° C. [1H NMR spectrum (300 MHz, (CD3)2SO-d6, δ in ppm): 0.83 (t, J=7.5 Hz: 3H); 1.43 (mt: 1H); 1.61 (mt: 1H); 2.70 (limiting AB: 2H); 3.40 (mt: 1H); 4.08 (mt: 1H); 6.28 (unresolved complex: 2H); 7.29 (broad d, J=5.5 Hz: 2H); 8.45 (broad d, J=5.5 Hz: 2H), (αD20=+166.9+/−2.4 at a concentration of 0.5% in methanol)].

Provenance & Evidence