تفاعل #44190

معادلة التفاعل

methylamine

Triethyl orthoformate

acetic anhydride

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

→

clean desired product

المردود 100.0%

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

المردود 100.0%

المذيبات

Water

diethyl ether

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةthe reaction mixture was cooled to room temperature
2. 2
   تركيزconcentrated under reduced pressure
3. 3
   درجة الحرارةThe residue was cooled to 0° C.
4. 4
   workup.STIRRINGthe reaction mixture stirred for 16 hours
5. 5
   استخلاصThe reaction mixture was extracted with ethyl acetate
6. 6
   استخلاصThe acidified aqueous layer was extracted with ethyl acetate
7. 7
   تجفيفThe combined organic extracts were dried (MgSO4)
8. 8
   تركيزconcentrated
9. 9
   أخرىto give a solid

الإجراء التجريبي

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).

المصدر