Acetone → 5-Thiazolemethanol, 2-amino--alpha-,-alpha--dimethyl-

Temperature

0 °C

Add n-Butyl lithium (1.6 M solution in hexane, 24 mL, 38 mmol, 2.0 eq.) in a dropwise manner at −78° C. under nitrogen to the solution of 2-amino thiazole (1.90 g, 18.97 mmol, 1.0 eq.) in anhydrous THF (80 mL). Add chlorotrimethyl silane (4.8 mL, 38 mmol, 2.0 eq.) to the mixture slowly at −78° C. Let the reaction mixture warm up to 0° C. slowly and stir the mixture at 0° C. for 10 minutes. Cool the solution to −78° C. and add n-Butyl lithium (1.6 M solution in hexane, 12 mL, 19 mmol, 1.0 eq.) in a dropwise manner. Add acetone (1.4 mL, 19 mmol, 1.0 eq.) last. Stir the reaction mixture at −78° C. for 10 minutes, then at room temperature for 30 minutes. Quench with ammonium chloride (sat. 10 mL) at −78° C. Then warm up to room temperature. Add ethyl acetate (200 mL). Wash the organic layer with aqueous saturated sodium chloride (3×30 mL), water (2×30 mL). Dry the organic phase over MgSO4 and filter the drying reagent off. Concentrate in vacuo. Purify by column chromatography (0%→5% methanol in dichloromethane→10% methanol in dichloromethane) to afford product (1.38 g, 46%). MS(ES), m/z 159 (M+1).

1. customslowly at −78° C
2. temperatureCool the solution to −78° C.
3. stirringStir the reaction mixture at −78° C. for 10 minutes
4. waitat room temperature for 30 minutes
5. customQuench with ammonium chloride (sat. 10 mL) at −78° C
6. temperatureThen warm up to room temperature
7. washWash the organic layer with aqueous saturated sodium chloride (3×30 mL), water (2×30 mL)
8. dry with materialDry the organic phase over MgSO4
9. filtrationfilter the drying reagent off
10. concentrationConcentrate in vacuo
11. customPurify by column chromatography (0%→5% methanol in dichloromethane→10% methanol in dichloromethane)

ORD record

ord-ea579db90e034c0d9c3239a4fc940f3f

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07666879B2