(5-BroMothiazol-2-yl)Methanol

To a solution of sodium borohydride (0.030 g, 0.781 mmol) in MeOH (2.0 mL) was added a solution of 5-bromothiazole-2-carbaldehyde (0.100 g, 0.521 mmol) in MeOH (1.00 mL) dropwise over a period of 5 min at room temperature. Upon the conclusion of this period, the reaction mixture was stirred at room temperature for 1 h. After this time, the solvent was removed in vacuo and the resulting residue was partitioned between EtOAc and water. The organic layer was separated and the aqueous phase was extracted with EtOAc. The combined organic layer was dried over anhydrous MgS000188] To a solution of sodium borohydride (0.030 g, 0.781 mmol) in MeOH (2.0 mL) was added a solution of 5-bromothiazole-2-carbaldehyde (0.100 g, 0.521 mmol) in MeOH (1.00 mL) dropwise over a period of 5 min at room temperature. Upon the conclusion of this period, the reaction mixture was stirred at room temperature for 1 h. After this time, the solvent was removed in vacuo and the resulting residue was partitioned between EtOAc and water. The organic layer was separated and the aqueous phase was extracted with EtOAc. The combined organic layer was dried over anhydrous MgS0Step 1 Preparation of 5-bromo-2-((triisopropylsilyloxy)methyl)thiazole A 100 mL round bottom flask is charged with 00188] To a solution of sodium borohydride (0.030 g, 0.781 mmol) in MeOH (2.0 mL) was added a solution of 5-bromothiazole-2-carbaldehyde (0.100 g, 0.521 mmol) in MeOH (1.00 mL) dropwise over a period of 5 min at room temperature. Upon the conclusion of this period, the reaction mixture was stirred at room temperature for 1 h. After this time, the solvent was removed in vacuo and the resulting residue was partitioned between EtOAc and water. The organic layer was separated and the aqueous phase was extracted with EtOAc. The combined organic layer was dried over anhydrous MgS04, filtered, and concentrated in vacuo to afford the title compound (0.067 g, 66% yield) as a dark oil. LCMS, [M+H]+ = 195.9.2, 4-DIBROMOTHIAZOLE (4.31 g, 17.7 mmol) are dissolved in anhydrous diethyl ether (170 ml) and the solution is cooled to-78 C (dry ice-acetone bath). n-Butyllithium (1.6 M in hexanes, 13 ml, 20.8 mmol) is added dropwise to the reaction mixture and the resulting solution is stirred at the same temperature for 30 minutes. Anhydrous DMF (ml, mmol) is then added at- 78 C and, after being stirred at the-78 C for 30 minutes, the reaction mixture is warmed to room temperature over a period of 2 hours. Hexanes (300 ml), were added and the resulting mixture is passed through a short silica cake eluting with 30% EtOAc-hexanes. The solvents are evaporated to yield the crude aldehyde which is used directly in the next step. To a solution of the above aldehyde in MeOH (80 NIL) is added sodium borohydride (g, MMOL), and the resulting mixture is stirred room temperature for hours. Hexanes (300 ml) are added and the mixture is passed through a short silica cake eluting with EtOAc. The crude alcohol is further purified by flash chromatography on silica with 20-50% EtOAc-hexanes as an eluant to yield g (MMOL, %) of the pure desired product.(4-Bromo-thiazol-2-yl)-methanol (L. LG, 5.7 mmol) in DMF (15 ml) is treated at room temperature under nitrogen atmosphere with TRIFLUOROMETHANESULFONYL chloride (0.61 ml, 1 equivalent), and Et3N (0.8 ml, 1 equivalent). The reaction mixture is stirred for 3 hours at room temperature before the addition of sodium azide (1. 11 g, 3 equivalents), followed by overnight stirring at the same temperature. The reaction mixture is diluted with water and extracted with DCM and diethyl ether. The combined organic extracts are dried (MGSO4) and concentrated under reduced pressure to afford the crude product, which is used without purification in the next step.

Molecular Weight:194.05
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:192.91970
Monoisotopic Mass:192.91970
Topological Polar Surface Area:61.4
Heavy Atom Count:8
Complexity:82.4
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes