Azetidine → 2-[2-(1-Azetidinyl)ethyl]-7-chloro-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one oxalate

HRID 364441Notes

Reaction equation

HRID 364441 reaction equation
[Cl:1][C:2]1[CH:12]=[N:11][C:10]2[O:9][CH:8]([CH2:13][CH2:14]Cl)[CH2:7][N:6]([CH3:16])[C:5](=[O:17])[C:4]=2[CH:3]=1.[C:18](=[O:21])([O-:20])[O-].[K+].[K+].[NH:24]1[CH2:27][CH2:26][CH2:25]1.[OH-:28].[NH4+]>CS(C)=O.O.CO.C(OCC)(=O)C>[C:5]([OH:17])(=[O:28])[C:18]([OH:20])=[O:21].[N:24]1([CH2:14][CH2:13][CH:8]2[CH2:7][N:6]([CH3:16])[C:5](=[O:17])[C:4]3[CH:3]=[C:2]([Cl:1])[CH:12]=[N:11][C:10]=3[O:9]2)[CH2:27][CH2:26][CH2:25]1

Participants

9

Reactant 4

HCID 10422Azetidine3×HCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 137264457-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H)-one

Product 1

HCID 137266002-[2-(1-Azetidinyl)ethyl]-7-chloro-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one oxalate

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6 g (0.022 mole) of 7-chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepine-5(4H)-one in 40 ml of dimethyl sulfoxide was added 8.0 g of crushed potassium carbonate and 1.5 g (0.026 mole) of azetidine. The reaction was stirred at room temperature for 24 hr. After checking ty TLC 7:2:1 by volume ethyl acetate:methanol:conc. ammonium hydroxide, another 0.4 g (0.007 mole) of azetidine was added. Two days later, another 0.5 g (0.0087 mole) of azetidine was added and the mixture stirred for 24 hr more. The reaction mixture was diluted with 100 ml of water and extracted with 4×100 ml of benzene. The organic extracts were combined, washed with 3×100 ml of water, dried over sodium sulfate, filtered, and concentrated by rotary evaporation. The syrupy residue was treated with oxalic acid in isopropyl alcohol. This yielded 4.2 g (56.5%) of white material, m.p. 169°-174° C. with decomposition.

Workup

  1. stirringthe mixture stirred for 24 hr more
  2. extractionextracted with 4×100 ml of benzene
  3. washwashed with 3×100 ml of water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. additionThe syrupy residue was treated with oxalic acid in isopropyl alcohol

Sources & evidence

ORD record
ord-f51e1e94325544908fc48554e2813929
Source dataset
uspto-grants-1986_08
Patent number
US04604388

Reaction notes

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