Triethylamine → 5-(Azetidin-1-ylcarbonyl)-2-bromo-4-methyl-1,3-thiazole

Oxalyl chloride (0.47 mL; 5.41 mmol) was added to a solution of 2-bromo-4-methyl-1,3-thiazole-5-carboxylic acid (1.0 g; 4.5 mmol) in DCM (25 mL). The mixture was stirred at RT for 18 hours, the DCM was evaporated in vacuo, the residue azeotroped with toluene (2×5 mL) and added to a solution of azetidine hydrochloride (503 mg; 5.41 mmol) and triethylamine (2.3 mL; 16.2 mmol) in DCM (50 mL). The mixture was stirred at RT for 18 hours, the DCM evaporated in vacuo, and the residue partitioned between water (75 mL) and ethyl acetate (150 mL). The organic layer was washed with brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 40% ethyl acetate in isohexane, to give a solid which was crystallised from ethyl acetate/isohexane to give the desired compound (490 mg). 1H NMR δ (CDCl3): 2.35 (m, 2H), 2.55 (s, 3H) and 4.1 (t, 4H).

1. customthe DCM was evaporated in vacuo
2. customthe residue azeotroped with toluene (2×5 mL)
3. stirringThe mixture was stirred at RT for 18 hours
4. customthe DCM evaporated in vacuo
5. customthe residue partitioned between water (75 mL) and ethyl acetate (150 mL)
6. washThe organic layer was washed with brine
7. dry with materialdried (MgSO4)
8. customevaporated to a residue which
9. customwas chromatographed on silica
10. washeluting with 40% ethyl acetate in isohexane
11. customto give a solid which
12. customwas crystallised from ethyl acetate/isohexane

ORD record

ord-8224941a690846769e7ef47b38d734bb

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07642259B2