Sodium hydride → HCID 86751982, compound

HRID 727269Notes

Reaction equation

HRID 727269 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([CH2:18][CH3:19])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[CH2:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH:27]([CH2:33][CH3:34])[C:28]([O:30][CH2:31][CH3:32])=[O:29]>C(=O)(OCC)OCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:14]3[CH:15]=[C:16]([CH2:18][CH3:19])[S:17][C:13]=3[N:12]3[C:20]([CH3:23])=[N:21][N:22]=[C:11]3[C:10]([CH2:34][CH2:33][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:9]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79039Butanoic acid, 2-bromo-, ethyl esterHCID 12434332HCID 12434332, compound

Product 1

HCID 86751982HCID 86751982, compound

Reagents, catalysts & solvents 1

HCID 7766Diethyl CarbonateSolvent

Procedure

4-(4-Chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (6 g) is dissolved in diethyl carbonate (100 ml) under a nitrogen stream, and 60% sodium hydride (1.2 g) is added with stirring at room temperature. The mixture is refluxed under heating for 1 hour and cooled to 50° C. with ice water. Ethyl bromobutyrate (4.3 ml) is added. After stirring at 100° C. for 2 hours, the reaction mixture is poured into ice water (1 l) and extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (ethyl acetate:methanol=100:l) and crystallized from isopropyl ether to give 3.9 g of (±)-ethyl 4-(4-(4-chlorophenyl)-6-ethoxycarbonyl-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)butyrate as white powdery crystals. (±)-Ethyl 4-(4-(4-chlorophenyl)-6-ethoxycarbonyl-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]-triazolo[4,3-a][1,4]diazepin-6-yl)butyrate (3.5 g) is dissolved in a mixture of ethanol (180 ml) and water (60 ml), and barium hydroxide 8 hydrate (8.4 g) is added. The mixture is refluxed under heating for 4 hours. After the completion of the reaction, ethanol is distilled away under reduced pressure and adjusted to pH 1 with 1N hydrochloric acid. The mixture is stirred for 30 minutes and adjusted to pH 4 with a saturated aqueous solution of sodium hydrogencarbonate to give 1.1 g of (±)-4-(4-(4-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)butyric acid as white powdery crystals, melting point 185°-187° C.

Workup

  1. additionis added
  2. temperatureThe mixture is refluxed
  3. temperatureunder heating for 1 hour
  4. stirringAfter stirring at 100° C. for 2 hours
  5. extractionextracted with ethyl acetate
  6. washThe organic layer is washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified by silica gel column chromatography (ethyl acetate:methanol=100:l)
  10. customcrystallized from isopropyl ether

Sources & evidence

ORD record
ord-dd8d92647c314b37aea2d2b862b022ce
Source dataset
uspto-grants-1998_01
Patent number
US05712274

Reaction notes

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