Ammonium Chloride → HCID 11594476, compound

Temperature

-78 °C

n-Butyllithium (1.6M in hexanes, 1.76 mL, 2.83 mmol) was added dropwise to a stirred solution of 2-bromothiazole (462 mg, 251 μL, 2.82 mmol) in dry THF (13 mL) at −78° C. under N2 and the reaction was stirred at −78° C. for 45 min. Separately, isopropylmagnesium chloride (2M in THF, 0.94 mL, 1.99 mmol) was added to a stirred solution of benzyl {(1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethyl}carbamate (500 mg, 1.88 mmol) in dry THF (4 mL) at −15° C. under N2. This solution was stirred for 15 min at −15° C. and was added dropwise to the above 2-lithiothiazole solution at −78° C. The reaction was allowed to warm to room temperature overnight and saturated NH4Cl (20 mL) and water (10 mL) were added and the mixture was extracted with EtOAc (3×30 mL). The combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient) to afford benzyl [(1S)-1-methyl-2-oxo-2-(1,3-thiazol-2-yl)ethyl]carbamate. Rf=0.28 (20% EtOAc in hexanes). LCMS calc.=291.1; found=291.3 (M+1)+. 1H NMR (600 MHz, CDCl3) δ 8.03 (s, 1H), 7.70 (d, J=3.1 Hz, 1H), 7.34-7.29 (m, 5H), 5.79 (d, J=6.6 Hz, 1H), 5.53-5.49 (m, 1H), 5.14-5.08 (m, 2H), 1.55 (d, J=6.4 Hz, 3H).

1. stirringThis solution was stirred for 15 min at −15° C.
2. temperatureto warm to room temperature overnight
3. extractionthe mixture was extracted with EtOAc (3×30 mL)
4. washThe combined extracts were washed with brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated in vacuo
7. customto give the crude product
8. customThis was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient)

ORD record

ord-2e865b4594964718867afda7fceb57ee

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735435B2