Reaktion #1350

Reaktionsgleichung

2-chlorobenzaldehyde

ethyl 4-chloroacetoacetate

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

→

title compound

Ausbeute 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

Ausbeute 17.6%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeMethanol was removed under reduced pressure
2. 2
   workup.DISSOLUTIONthe residue dissolved in ethyl acetate (400 mL)
3. 3
   WaschenThe organic phase was washed with brine
4. 4
   Trocknendried (sodium sulfate)
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigePurification 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

Vorschrift

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.

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