N-[(1R,2R)-1-benzyl-2-hydroxypropyl]-N'-tert-butylthiourea → HCID 69698414, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 6.5 g of N-[(1R,2R)-1-benzyl-2-hydroxypropyl]-N′-tert-butylthiourea (diastereoisomer B) in 77 cm3 of 6N hydrochloric acid is heated at a temperature in the region of 100° C. for 10 hours. The reaction medium is then concentrated under reduced pressure (2 kPa) at a temperature in the region of 40° C. to give a yellow oil which is taken up in 100 cm3 of water. This aqueous phase is washed with twice 50 cm3 of dichloromethane and is then basified to a pH in the region of 10 by addition of 5 cm3 of concentrated sodium hydroxide. The resulting mixture is then extracted with 3 times 50 cm3 of dichloromethane. The combined organic phases are dried over sodium sulfate, filtered and then concentrated under reduced pressure (2 kPa) at a temperature in the region of 40° C. 4.09 g of (+)-(4R,5R)-4-benzyl-5-methyl-4,5-dihydro-1,3-thiazol-2-ylamine are obtained in the form of white crystals melting at 89° C. [1H NMR spectrum (300 MHz, (CD3)2SO-d6, δ in ppm): 1.22 (d, J=7 Hz: 3H); 2.66 (dd, J=13 and 7 Hz: 1H); 2.76 (dd, J=13 and 7 Hz: 1H); 3.54 (mt: 1H); 3.95 (mt: 1H); from 5.60 to 6.45 (unres. mult.: 2H); from 7.10 to 7,40 (mt: 5H). The relative stereochemistry in positions 4 and 5 was validated by NOE. A strong response of the proton H4 is noted after irradiating the methyl; (αD20=+83.9±1.3 at a concentration of 0.5% in methanol)].

Provenance & Evidence