1,3-Dichloroacetone → 4-([4-(Chloromethyl)-1,3-thiazol-2-yl]methyl}morpholine hydrochloride

2-Morpholin-4-ylethanethioamide (0.403 g, 2.52 mmol), 1,3-dichloroacetone (0.353 g, 2.77 mmol) and sodium bicarbonate (0.234 g, 2.77 mmol) was stirred in 1,2-dichloroethane (4 mL) at room temperature for 74 h at which point 1,4-dioxane was added in an attempt to improve solubility and the mixture was stirred for a further 30 h. The reaction mixture was filtered and the filter cake was washed with 1,2-dichloroethane. The filtrate was added dropwise to a cooled (ice bath) solution of thionyl chloride (0.202 mL, 2.77 mmol) in 1,2-dichloroethane (3 mL). The solution was stirred at 70° C. for 0.5 h and then cooled to room temperature. The brown mixture was filtered and washed with 1,2-dichloroethane to afford 4-{[4-(chloromethyl)-1,3-thiazol-2-yl]methyl}morpholine hydrochloride as a very pale brown solid (0.024 g, 0.091 mmol, 4% yield). 1H NMR (400 MHz; D2O): 3.29-3.39 (m, 4H); 3.78-3.92 (m, 4H); 4.63 (s, 2H); 4.67 (s, 2H); 7.67 (s, 1H); MS (EI) for C9H13ClN2OS: 233 (MH+).

1. additionwas added in an attempt
2. filtrationThe reaction mixture was filtered
3. washthe filter cake was washed with 1,2-dichloroethane
4. additionThe filtrate was added dropwise to
5. stirringThe solution was stirred at 70° C. for 0.5 h
6. filtrationThe brown mixture was filtered
7. washwashed with 1,2-dichloroethane

ORD record

ord-ed1d27a2c3774735abe1f88edc6f1064

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09163006B2