Potassium Carbonate → (E)-but-2-enedioic acid;4-methyl-2-[2-(2-methylpyrrolidin-1-yl)ethyl]-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione;propan-2-ol

HRID 1194245Notes

Reaction equation

HRID 1194245 reaction equation
Cl[CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH3:11])[C:8](=[S:12])[C:7]2[CH:13]=[CH:14][CH:15]=[N:16][C:6]=2[O:5]1.[CH3:17][CH:18]1[CH2:22][CH2:21][CH2:20][NH:19]1.C(=O)([O-])[O-].[K+].[K+].[C:29]([OH:36])(=[O:35])/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33]>C(O)C>[CH3:3][CH:4]([OH:5])[CH3:10].[C:29]([OH:36])(=[O:35])/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33].[CH3:11][N:9]1[C:8](=[S:12])[C:7]2[CH:13]=[CH:14][CH:15]=[N:16][C:6]=2[O:5][CH:4]([CH2:3][CH2:2][N:19]2[CH2:20][CH2:21][CH2:22][CH:18]2[CH3:17])[CH2:10]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 130032-MethylpyrrolidineHCID 444972Fumaric AcidHCID 137264422-(chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepine-5(4H)thione

Product 1

HCID 14391511(E)-but-2-enedioic acid;4-methyl-2-[2-(2-methylpyrrolidin-1-yl)ethyl]-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione;propan-2-olYield 32.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 5.0 g (0.019 mole) of 2-(chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepine-5(4H)-thione in 25 ml of absolute ethanol was added 3.5 g (0.04 mole) of 2-methylpyrrolidine. The mixture was heated to reflux for 6.5 hr and left standing at room temperature overnight. Mass spec and TLC showed presence of starting materials. Approximately 5 g of potassium carbonate was added and heating at reflux was continued for 24 hr. Ethanol was removed by rotary evaporation (70° C., 30 mm). The residue was taken up in 100 ml of methylene chloride and washed with 2×50 ml dil. aqueous sodium hydroxide. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation (70° C., 30 mm). The residual syrup was dissolved in isopropyl aocohol and treated with fumaric acid affording 4.5 g (0.01 mole, 49.2%) of crude crystals. Two recrystallizations from isopropyl afforded 1.5 g (16.4%) of yellow crystals, m.p., 92°-95° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 6.5 hr
  3. waitleft
  4. temperatureheating
  5. temperatureat reflux
  6. waitwas continued for 24 hr
  7. customEthanol was removed by rotary evaporation (70° C., 30 mm)
  8. washwashed with 2×50 ml dil. aqueous sodium hydroxide
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated by rotary evaporation (70° C., 30 mm)
  12. dissolutionThe residual syrup was dissolved in isopropyl aocohol
  13. customTwo recrystallizations from isopropyl

Sources & evidence

ORD record
ord-b3a258b51e67433494da4c07c53c31ad
Source dataset
uspto-grants-1989_03
Patent number
US04812565

Reaction notes

Loading…