Pyridine → (R)-N-(2-Chlorophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide

온도

80 °C

Acetyl chloride (11.7 ml, 164 mmol) was added dropwise to a stirred solution of the (R)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (Method 9) (10 g, 63 mmol) in toluene (100 ml) cooled in an ice bath. The mixture was then heated to 80° C. and the suspension dissolved to yield a clear solution. After 2 h the reaction mixture was cooled and then concentrated to yield a slight brown oil. This oil was then redissolved in DCM (140 ml) and DMF (4 drops) was added followed by oxalyl chloride (6 ml, 69 mmol). The solution bubbled vigorously and the reaction mixture was left to stir. After 15 h, this reaction mixture was added slowly to a stirred solution of 2-chloroaniline (8.7 g, 68 mmol) and pyridine (5.5 ml, 68 mmol) in DCM (150 ml). After 15 h stirring at room temperature, the resultant mixture was concentrated and the residue dissolved in methanol (500 ml). A solution of lithium hydroxide monohydrate (7.8 g, 0.19 mol) in water (120 ml) was then added and the mixture was stirred for 4 h. The mixture was then concentrated and the residue acidified to pH 2 (by addition of concentrated hydrochloric acid). Ethyl acetate(150 ml) was added and the mixture washed with water (2×100 ml) and brine, dried and evaporated to dryness. The residue was purified by flash column chromatography using 6:1, iso-hexane:ethyl acetate to yield the title compound as a white solid (13.8 g, 52 mmol). NMR: 1.6 (s, 3H), 7.1-7.25 (m, 1H), 7.3-7.4 (m, 1H), 7.55 (dd, 1H), 7.8 (s, 1H), 8.0 (dd, 1H), 9.7 (brs, 1H); MS: 266.

1. temperaturecooled in an ice bath
2. dissolutionthe suspension dissolved
3. customto yield a clear solution
4. temperatureAfter 2 h the reaction mixture was cooled
5. concentrationconcentrated
6. customto yield a slight brown oil
7. customThe solution bubbled vigorously
8. waitthe reaction mixture was left
9. stirringAfter 15 h stirring at room temperature
10. concentrationthe resultant mixture was concentrated
11. dissolutionthe residue dissolved in methanol (500 ml)
12. stirringthe mixture was stirred for 4 h
13. concentrationThe mixture was then concentrated
14. additionthe residue acidified to pH 2 (by addition of concentrated hydrochloric acid)
15. additionEthyl acetate(150 ml) was added
16. washthe mixture washed with water (2×100 ml) and brine
17. customdried
18. customevaporated to dryness
19. customThe residue was purified by flash column chromatography

ORD 기록

ord-43c4f0d07cd04672983e9574856a56e8

출처 데이터셋

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06960688B2