Thionyl Chloride → HCID 14098472, compound

HRID 247299Notes

Reaction equation

HRID 247299 reaction equation
[Na].[S:2](Cl)(Cl)=O.[Cl:6][CH2:7][CH2:8][CH:9]1[CH2:15][N:14]([CH3:16])[C:13](=O)[C:12]2[CH:18]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:20]=[N:21][C:11]=2[O:10]1>C1(C)C=CC=CC=1>[Cl:6][CH2:7][CH2:8][CH:9]1[CH2:15][N:14]([CH3:16])[C:13](=[S:2])[C:12]2[CH:18]=[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:20]=[N:21][C:11]=2[O:10]1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 5360545SodiumHCID 14404275HCID 14404275, compound

Product 1

HCID 14098472HCID 14098472, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The entire portion of the above sodium salt was added ~400 ml of thionyl chloride slowly (reaction was slightly exothermic) and stirred at room temperature for 10 minutes. The thionyl chloride was removed by rotary evaporation at 70° C. and the residue azeotroped once with toluene. The residue was suspended in 600 ml of methylene chloride and to the suspension was added diisopropylethylamine cautiously until the solution was basic. The reaction solution was washed with 3×200 ml of 1N hydrochloric acid and 3×200 ml of 1N sodium hydroxide, dried over sodium sulfate, filtered, concentrated by rotary evaporation, taken up in toluene, charcoaled twice and concentrated by rotary evaporation. The residue (60 g) was taken up in ethyl acetate and passed through a short bed of silica gel using 25% hexane-75% ethyl acetate as the eluant. Similar fractions were combined to give ~25 g of crude (but 95% (min)) purity oil which is 2-(2-chloroethyl)-2,3-dihydro-4-methyl-7-phenylpyrido[3,2-f] -1,4-oxazepin-5(4H)-one. To 12.5 g (0.04 mole) of the above amide was added 125 ml of toluene and 16 g (0.04 mole) of 2,4-bis(4-methoxyphenyl)-1,3-dithio-2,4-diphosphotane-2,4-disulfide. The reaction mixture was heated to reflux for 4 hr. After standing overnight, the toluene was decanted off, washed with 3×100 ml of 1N sodium hydroxide, dried over sodium sulfate, filtered, and concentrated by rotary evaporation. The residue was further purified by column chromatography using silica gel as the stationary phase and eluting with ethyl acetate: hexane 1:1, (v/v). Like fractions were combined and concentrated giving 8.5 g (64%) of desired product, m.p. 156°-58° C.

Workup

  1. customreaction
  2. customThe thionyl chloride was removed by rotary evaporation at 70° C.
  3. customthe residue azeotroped once with toluene
  4. additionwas added diisopropylethylamine cautiously until the solution
  5. washThe reaction solution was washed with 3×200 ml of 1N hydrochloric acid and 3×200 ml of 1N sodium hydroxide
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporation
  9. concentrationconcentrated by rotary evaporation
  10. customto give ~25 g of crude (but 95% (min)) purity oil which
  11. temperatureThe reaction mixture was heated
  12. temperatureto reflux for 4 hr
  13. waitAfter standing overnight
  14. customthe toluene was decanted off
  15. washwashed with 3×100 ml of 1N sodium hydroxide
  16. dry with materialdried over sodium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated by rotary evaporation
  19. customThe residue was further purified by column chromatography
  20. washeluting with ethyl acetate: hexane 1:1, (v/v)
  21. concentrationconcentrated

Sources & evidence

ORD record
ord-c03e5019165e42dcb6eb12333d76c658
Source dataset
uspto-grants-1987_11
Patent number
US04705853

Reaction notes

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