反応 #1350

反応方程式

2-chlorobenzaldehyde

ethyl 4-chloroacetoacetate

3-(2-hydroxyethylamino)-but-2-enoic acid methyl ester

→

title compound

収率 17.6%

5-Chloromethyl-7-(2-chlorophenyl)-8a-methyl-3,7,8,8a-tetrahydro-2H-oxazolo[3,2-a]pyridine-6,8-dicarboxylic acid 6-ethyl 8-methyl ester

収率 17.6%

溶媒

methanol

反応条件

後処理

1. 1
   その他Methanol was removed under reduced pressure
2. 2
   workup.DISSOLUTIONthe residue dissolved in ethyl acetate (400 mL)
3. 3
   洗浄The organic phase was washed with brine
4. 4
   乾燥dried (sodium sulfate)
5. 5
   ろ過filtered
6. 6
   濃縮concentrated in vacuo
7. 7
   その他Purification of the residue by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å)
8. 8
   workup.ADDITIONa solvent mixture of hexane and ethyl acetate as eluent (95:5, 90:10, 85:15, 80:20, 70:30 and 60:40) as eluent

実験手順

A mixture of 2-chlorobenzaldehyde (XI, 57.0 g), ethyl 4-chloroacetoacetate (VIII, 69.3 g) and 3-(2-hydroxyethylamino)-but-2-enoic acid methyl ester (XXIII, 63.2 g) in methanol (800 mL) was stirred at room temperature for 48 h. Methanol was removed under reduced pressure and the residue dissolved in ethyl acetate (400 mL). The organic phase was washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a solvent mixture of hexane and ethyl acetate as eluent (95:5, 90:10, 85:15, 80:20, 70:30 and 60:40) as eluent afforded the title compound (XXIV 30.0 g). 1H-NMR (CDCl3) δ (ppm): 0.80 (t, 3H, J=6.9 Hz), 1.05 (s, 3H), 3.73 (s, 3H), 3.39 (s, 1H), 3.74-4.09 (m, 4H), 4.06 (q, 2H, J=6.9 Hz), 4.51 (d, 1H, J=11.5 Hz),4.63 (s, 1H), 5.40 (d, 1H, J=11.5 Hz), 7.12-7.40 (m, 4H); 13C-NMR (CDCl3) δ (ppm): 13.6, 25.7, 39.3, 39.7, 45.8, 51.0, 51.7, 59.5, 63.4, 90.5, 98.6, 126.3, 126.8, 129.6, 129.9, 133.6, 140.7, 149.5, 167.5, 171.8; HRMS: calc. for C20H23Cl2 NO2 427.0953 found 427.0939; Elemental Analysis (%): calc. (found) C 56.09 (56.12), H 5.41 (5.26), N 3.27 (3.07); m.p. 141.9°-142.8° C.; IR(KBr, cm-1): 1742, 1676, 1581, 1566.

出典