Methoxyacetone → 4-(Methoxymethyl)-1,3-thiazol-2-amine

Temperature

0 °C

A solution of 1-methoxypropan-2-one (20.3 g, 231 mmol) in 200 mL of MeOH was added to a 250 mL round-bottom flask. The flask was then immersed in an ice-water bath. Br2 was added dropwise to the reaction mixture through an addition funnel. After the addition, the addition funnel was rinsed with 50 mL MeOH, and the reaction mixture was stirred for 20 minutes at 0° C. The ice-water bath was then removed, and the reaction mixture was stirred for two more hours. Thiourea (18 g, 231 mmol) was then added to the reaction mixture, and the reaction was heated at reflux overnight. The reaction was concentrated, and saturated sodium bicarbonate and solid sodium carbonate were used to adjust the pH to 8-9. The resulting mixture was then extracted three times with 200 mL portions of EtOAc. The organic layers were concentrated and then purified by recrystallization to give 4-(methoxymethyl)thiazol-2-amine (11 g, 33% yield over two steps). MS m/z: 145 (M+1).

1. customThe flask was then immersed in an ice-water bath
2. additionAfter the addition
3. washthe addition funnel was rinsed with 50 mL MeOH
4. customThe ice-water bath was then removed
5. stirringthe reaction mixture was stirred for two more hours
6. temperaturethe reaction was heated
7. temperatureat reflux overnight
8. concentrationThe reaction was concentrated
9. extractionThe resulting mixture was then extracted three times with 200 mL portions of EtOAc
10. concentrationThe organic layers were concentrated
11. custompurified by recrystallization

ORD record

ord-6812f5879b00413b99c14227fc5f2a88

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07514566B2