2-Aminothiazole → 1-(2-Amino-1,3-thiazol-5-yl)cyclobutan-1-ol

Temperature

-60 °C

A solution of 2-aminothiazole (7.1 g, 71 mmol) in THF (360mL) cooled to −78° C. was treated dropwise with n-BuLi (56.18 mL, 142 mmol) while maintaining an internal temperature less than or about equal to −60° C. After addition was completed, the solution was treated dropwise with chlorotrimethylsilane (18 mL, 142 mmol). The reaction solution was warmed to −10° C., then was cooled back to −78° C. n-Butyllithium (28.4 mL, 71 mmol) was added dropwise and after 10 minutes, cyclobutanone (5.33 mL, 71 mmol) was added dropwise. The solution was stirred for 1 hour at −78° C., was quenched with saturated ammonium chloride solution, and was warmed to 23° C. The reaction mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with brine, was dried (MgSO4), was filtered, and solvent was removed in vacuo. The resulting residue was purified by silica gel chromatography (15:1→7:1 CHCl3—MeOH) to afford 7.24 g of 1-(2-amino-thiazol-5-yl)cyclobutanol. 1HNMR (400 MHz, DMSO-D6) δ 6.78 (s, 1H), 6.70 (s,2H), 5.58 (s,1H), 22 (m,4H), 1.69 (m, 1H), 1.50 (m,1H).

1. additionAfter addition
2. temperatureThe reaction solution was warmed to −10° C.
3. additionwas added dropwise and after 10 minutes
4. customwas quenched with saturated ammonium chloride solution
5. temperaturewas warmed to 23° C
6. extractionThe reaction mixture was extracted with ethyl acetate (300 mL)
7. washThe organic layer was washed with brine
8. dry with materialwas dried (MgSO4)
9. filtrationwas filtered
10. customsolvent was removed in vacuo
11. customThe resulting residue was purified by silica gel chromatography (15:1→7:1 CHCl3—MeOH)

ORD record

ord-1662344927d84a85a0b6189a822e60b0

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06720427B2