反应 #44190

反应方程式

methylamine

Triethyl orthoformate

acetic anhydride

2-methyl-3-oxo-pentanedioic acid diethyl ester

→

clean desired product

收率 100.0%

4-hydroxy-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester

收率 100.0%

溶剂

Water

diethyl ether

反应条件

后处理

1. 1
   温度the reaction mixture was cooled to room temperature
2. 2
   浓缩concentrated under reduced pressure
3. 3
   温度The residue was cooled to 0° C.
4. 4
   workup.STIRRINGthe reaction mixture stirred for 16 hours
5. 5
   萃取The reaction mixture was extracted with ethyl acetate
6. 6
   萃取The acidified aqueous layer was extracted with ethyl acetate
7. 7
   干燥The combined organic extracts were dried (MgSO4)
8. 8
   浓缩concentrated
9. 9
   其他to give a solid

实验过程

Triethyl orthoformate (3.85 mL, 23.12 mmol) and acetic anhydride (4.37 mL, 46.25 mmol) were added to 2-methyl-3-oxo-pentanedioic acid diethyl ester (Caliskan et al Aust. J. Chem. 1999, 52 (11), 1013-1020) (5.0 g, 23.1 mmol) and the reaction mixture heated to 135° C. After 1 hour, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was cooled to 0° C. and methylamine (40% in water, 5.0 mL, 57.81 mmol) was added with stirring. Water (20 mL) was added and the reaction mixture stirred for 16 hours. The reaction mixture was extracted with ethyl acetate and the aqueous layer acidified to pH 2 with 10% aqueous HCl. The acidified aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried (MgSO4) and concentrated to give a solid. Trituration with diethyl ether yielded 4.88 g (55%) clean desired product. 4-Hydroxy-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester was carried forward as described in Example 1, Steps B-D. MS APCI (−) m/z 353, 355 (M−, Br pattern) detected; 1H NMR (400 MHz, CD3OD) δ 8.49 (s, 1H), 7.36 (dd, 1H), 7.24 (dd, 1H), 6.71 (m, 1H), 3.60 (s, 3H), 1.68 (s, 3H).

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