Triethylamine → (Azetidin-1-yl)(2-bromo-1,3-thiazol-4-yl)methanone

To a solution of 2-bromothiazole-5-carboxylic acid (752 mg, 3.62 mmol) in DCM (10 mL) was slowly added oxalyl chloride (0.38 mL, 4.34 mmol) and then DMF (1 drop). The mixture was stirred for 4 hours, following which the organics were removed in vacuo, and the residues azeotroped with toluene (10 mL). The crude material was dissolved in DCM (10 mL) and slowly added to a stirred suspension of azetidine hydrochloride (404 mg, 4.34 mmol) and triethylamine (1.8 mL, 13 mmol) in DCM (25 mL). The mixture was stirred at RT for 2 hours before the organics were removed in vacuo. The residue was partitioned between ethyl acetate (50 mL) and water (25 mL), the organic layer washed with brine (25 mL), dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 40% ethyl acetate in iso-hexane, to give the desired compound (500 mg).

1. customorganics were removed in vacuo
2. customthe residues azeotroped with toluene (10 mL)
3. dissolutionThe crude material was dissolved in DCM (10 mL)
4. stirringThe mixture was stirred at RT for 2 hours before the
5. customorganics were removed in vacuo
6. customThe residue was partitioned between ethyl acetate (50 mL) and water (25 mL)
7. washthe organic layer washed with brine (25 mL)
8. dry with materialdried (MgSO4)
9. customevaporated to a residue which
10. customwas chromatographed on silica
11. washeluting with 40% ethyl acetate in iso-hexane

ORD record

ord-feb4c08ee1d04a7d91f20b194cfcb0ff

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07642259B2