Morpholine → Tert-butyl 4-(morpholinomethyl)thiazol-2-ylcarbamate

Temperature

0 °C

tert-Butyl 4-(hydroxymethyl)thiazol-2-ylcarbamate (57; 2.0 g, 8.7 mmol) was taken up in 25 mL of CH2Cl2 along with Et3N (1.82 mL, 13.05 mmol) and cooled to 0° C. Methanesulfonyl chloride (0.85 mL, 10.88 mmol) was added and the resulting reaction mixture was stirred at 0° C. for 60 min. Morpholine (48; 3.0 mL, 35 mmol) was then added and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated under reduced pressure. The resulting residue was taken up in EtOAc and washed with dilute aqueous NaHCO3, brine, dried (Na2SO4) and concentrated under reduced pressure. This material was purified by filtering through a short column of silica gel. The filtrate was concentrated to afford 1.88 g of tert-butyl 4-(morpholinomethyl)thiazol-2-ylcarbamate 58. The Boc group was removed by treating tert-butyl 4-(morpholinomethyl)thiazol-2-ylcarbamate 58 with 20 mL of 25% TFA in CH2Cl2 for 18 h at room temperature. After all the solvent had been removed by concentrating and drying under high vacuum, the resulting residue was treated with a mixture of pentane/EtOAc to afford 2.17 g 4-(morpholinomethyl)thiazol-2-amine 59 as a white solid.

1. customthe resulting reaction mixture
2. stirringthe reaction mixture was stirred at room temperature for 18 h
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. washwashed with dilute aqueous NaHCO3, brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated under reduced pressure
7. customThis material was purified
8. filtrationby filtering through a short column of silica gel
9. concentrationThe filtrate was concentrated

ORD record

ord-0eca660808a84c11a62aa52bf2ea89e5

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846947B2