Acetic Acid → Methyl 3-(2-Chloro-5-(4-morpholinylmethyl)-3-thienyl)-3-oxopropanoate

HRID 411244Notes

Reaction equation

HRID 411244 reaction equation
[Cl:1][C:2]1[S:3][C:4]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:5][C:6]=1[C:7](=[O:9])[CH3:8].[H-].[Na+].C(O)(=O)C.[CH3:23][O:24][C:25](=O)[O:26]C>>[Cl:1][C:2]1[S:3][C:4]([CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:5][C:6]=1[C:7](=[O:9])[CH2:8][C:25]([O:24][CH3:23])=[O:26]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 12021Dimethyl CarbonateHCID 24758Sodium hydrideHCID 223972051-(2-Chloro-5-(4-morpholinylmethyl)-3-thienyl)ethanone

Product 1

HCID 22397221Methyl 3-(2-Chloro-5-(4-morpholinylmethyl)-3-thienyl)-3-oxopropanoateYield 41%

Conditions

Temperature
95 °C

Procedure

To a solution of 1-(2-chloro-5-(4-morpholinylmethyl)-3-thienyl)ethanone (Preparation 63, 9.53g) in dimethylcarbonate (200 mL) is added NaH (1.53 g; 60% dispersion in mineral oil) portionwise at ambient temperature. The reaction mixture is heated to 95° C. for 3 h. The reaction vessel is cooled to ambient temperature and the mixture is poured into ice cold water (500 mL) containing acetic acid (15 mL). The aqueous layer is extracted with Et2O (3×100 mL). The organic layer is separated, dried over MgSO4, filtered, and concentrated in vacuo. The crude brown liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc) to afford 4.77g (41%) of the title compound as a tan solid. Physical characteristics: m.p. 67-68° C.; 1H NMR (300 MHz, CDCl3) δ 7.21, 3.99, 3.78, 3.71, 3.60, 2.50; IR (diffuse reflectance) 2822, 1738, 1663, 1461, 1399, 1350, 1336, 1316, 1286, 1265, 1156, 1113, 1009, 1004, 864 cm−1; MS (ESI+) m/z 318; Anal. Found: C, 48.89; H, 5.13; N, 4.45.

Workup

  1. temperatureThe reaction vessel is cooled to ambient temperature
  2. extractionThe aqueous layer is extracted with Et2O (3×100 mL)
  3. customThe organic layer is separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude brown liquid is purified by silica gel column chromatography (4/1, hexanes/EtOAc)

Sources & evidence

ORD record
ord-f76d14a9a7a5488a873725dd1a75c404
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

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