Potassium Hydroxide → 2-(Chloromethyl)-4-ethyl-1,3-benzothiazole

(Method J) A solution of 4-ethyl-1,3-benzothiazol-2-amine (1.0 g, 5.6 mmol, 1 equiv.) and KOH (7.4 g, 112.2 mmol, 20 equiv.) in 2-methoxy-ethanol (9 ml) and H2O (9 ml), was stirred under N2 and under reflux, for 20 h. After cooling at r.t., the mixture was poured into water (150 ml) and extracted with CH2Cl2 (2×40 ml). The aqueous phase was neutralised with conc. HCl and extracted again with CH2Cl2 (3×70 ml). The combined neutral extracts were washed with water (2×60 ml), dried (Na2SO4) and evaporated to dryness under reduced pressure. The yellow-green semi-solid residue (790 mg) was mixed with 2-chloro-1,1,1-trimethoxy ethane (1.62 g, 10.4 mmol) and the mixture was stirred, under N2, at 60° C., for 4 h. Volatiles were removed by evaporation under reduced pressure and the brown liquid residue was purified by column chromatography on silica, eluted with CH2Cl2/hexane (10% and 50%), to give a yellow liquid (406 mg, 34% yield over two steps). HPLC-MS (method 1): m/z 212 [M+H]+, Rt=5.00 min

1. temperatureunder reflux, for 20 h
2. extractionextracted with CH2Cl2 (2×40 ml)
3. extractionextracted again with CH2Cl2 (3×70 ml)
4. washThe combined neutral extracts were washed with water (2×60 ml)
5. dry with materialdried (Na2SO4)
6. customevaporated to dryness under reduced pressure
7. customVolatiles were removed by evaporation under reduced pressure
8. customthe brown liquid residue was purified by column chromatography on silica
9. washeluted with CH2Cl2/hexane (10% and 50%)
10. customto give a yellow liquid (406 mg, 34% yield over two steps)

ORD-Eintrag

ord-98dfd3a2bd7b4f3b8c4a1aa81c0bc3d3

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08088791B2