Dimethyl Sulfoxide → HCID 11757972, compound

HRID 358785Notes

Reaction equation

HRID 358785 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][O:12][C:13]1[C:14]([O:47][CH3:48])=[CH:15][C:16]2[CH2:22][CH2:21][CH2:20][C:19]([C:23]([N:25]3[CH2:30][CH2:29][N:28]([CH2:31][C:32]4[CH:37]=[C:36]([O:38][CH3:39])[C:35]([O:40][CH3:41])=[C:34]([O:42][CH3:43])[CH:33]=4)[CH2:27][CH:26]3[CH2:44]O)=[O:24])=[CH:18][C:17]=2[CH:46]=1.[CH2:49]([N:51](CC)[CH2:52][CH3:53])[CH3:50]>C(Cl)Cl>[CH2:49]([N:51]([CH2:44][CH:26]1[CH2:27][N:28]([CH2:31][C:32]2[CH:33]=[C:34]([O:42][CH3:43])[C:35]([O:40][CH3:41])=[C:36]([O:38][CH3:39])[CH:37]=2)[CH2:29][CH2:30][N:25]1[C:23]([C:19]1[CH2:20][CH2:21][CH2:22][C:16]2[CH:15]=[C:14]([O:47][CH3:48])[C:13]([O:12][CH3:11])=[CH:46][C:17]=2[CH:18]=1)=[O:24])[CH2:52][CH3:53])[CH3:50]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 10436901HCID 10436901, compound

Product 1

HCID 11757972HCID 11757972, compoundYield 27.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of oxalyl chloride (360 mg) in methylene chloride (5 ml) is added dropwise at -78° C. a (340 mg) solution of dimethyl sulfoxide (340 mg) in methylene chloride (2 ml), and the mixture is stirred for 10 minutes. To the resulting reaction mixture is added dropwise a solution of 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl) -4-(3,4,5-trimethoxybenzyl)piperazine-2-methanol (750 mg) in methylene chloride (2 ml), then the mixture is stirred for 15 minutes. To the reaction mixture is added triethylamine (1 g), then the reaction temperature is raised up to room temperature. The reaction mixture is poured into ice-water, followed by extraction with methylene chloride. The organic layer is washed with water, dried and concentrated under reduced pressure. The concentrate is dissolved in methanol (10 ml). To the solution is added diethylamine hydrochloride (1.4 g), and the mixture is stirred for 3 hours at 50° C. To the reaction mixture is added, after cooling, sodium cyanoborohydride (90 mg), followed by stirring for one hour at room temperature. The reaction mixture is poured into ice-water, followed by extraction with methylene chloride. The organic layer is washed with water, dried and concentrated under reduced pressure. The concentrate is purified by means of a silica gel column chromatography (eluent:ethyl acetate-methanol=9:1) to give 2-diethylaminomethyl-1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl) -4-(3,4,5-trimethoxybenzyl)piperazine (230 mg). This product is converted to its hydrochloride, followed by recrystallization from ethanol to give colorless crystals, m.p. 157-160° C.

Workup

  1. customTo the resulting reaction mixture
  2. stirringthe mixture is stirred for 15 minutes
  3. extractionfollowed by extraction with methylene chloride
  4. washThe organic layer is washed with water
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe concentrate is dissolved in methanol (10 ml)
  8. additionTo the solution is added diethylamine hydrochloride (1.4 g)
  9. stirringthe mixture is stirred for 3 hours at 50° C
  10. additionTo the reaction mixture is added
  11. temperatureafter cooling
  12. stirringby stirring for one hour at room temperature
  13. additionThe reaction mixture is poured into ice-water
  14. extractionfollowed by extraction with methylene chloride
  15. washThe organic layer is washed with water
  16. customdried
  17. concentrationconcentrated under reduced pressure
  18. customThe concentrate is purified by means of a silica gel column chromatography (eluent:ethyl acetate-methanol=9:1)

Sources & evidence

ORD record
ord-2099d039df644d2fb77d7aa97c3725d0
Source dataset
uspto-grants-1991_03
Patent number
US04997836

Reaction notes

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