Hydrochloric Acid → 2-[2-(3,4-Dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl 4-nitrobenzenesulfonate

HRID 227546Notes

Reaction equation

HRID 227546 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:15][CH2:16][OH:17])[O:14][CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(N(CC)CC)C.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:33]=[C:34]([O:38][CH3:39])[C:35]=1[O:36][CH3:37])[C:30](Cl)=[O:31].CN(C1C=CC=CN=1)C.[N+:49]([C:52]1[CH:57]=[CH:56][C:55]([S:58](Cl)(=[O:60])=[O:59])=[CH:54][CH:53]=1)([O-:51])=[O:50].Cl>C(Cl)Cl.O>[N+:49]([C:52]1[CH:53]=[CH:54][C:55]([S:58]([O:17][CH2:16][CH2:15][C:9]2([C:4]3[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=3)[O:14][CH2:13][CH2:12][N:11]([C:30](=[O:31])[C:29]3[CH:28]=[C:27]([O:26][CH3:25])[C:35]([O:36][CH3:37])=[C:34]([O:38][CH3:39])[CH:33]=3)[CH2:10]2)(=[O:60])=[O:59])=[CH:56][CH:57]=1)([O-:51])=[O:50]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 74044-Nitrobenzenesulfonyl chlorideHCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 154727472-[2-(3,4-Dichlorophenyl)morpholin-2-YL]ethanol

Product 1

HCID 112159572-[2-(3,4-Dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl 4-nitrobenzenesulfonateYield 94.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
2.5 °C

Procedure

To a solution of 2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol (5 g, 18.0 mmol) in methylene chloride (25 ml) was added triethylamine (7.5 ml, 54.0 mmol) under a nitrogen stream, the resulting mixture was cooled to 0-5° C., then a solution of 3,4,5-trimethoxybenzoyl chloride (4.2 g, 18.4 mmol) in methylene chloride (20 ml) was further added dropwise at below 10° C. After the resulting mixture was stirred at 0-5° C. for one hour, dimethylaminopyridine (0.22 g, 1.8 mmol) was further added. Subsequently, a solution of 4-nitrobenzenesulfonyl chloride (4.8 g, 21.6 mmol) in methylene chloride (10 ml) was further added dropwise at below 10° C., and the resulting mixture was stirred at room temperature for 30 minutes. After completion of the reaction, to the reaction mixture were added successively water (50 ml) and concentrated hydrochloric acid (5 ml), and the resulting mixture was partitioned. The separated organic layer was washed with water twice (50 ml each) and evaporated to dryness. Subsequently, to the obtained residue was added toluene (45 ml), and the resulting mixture was refluxed to dissolve the residue. The solution thus obtained was cooled to 0-5° C. over about one hour, and stirred at the same temperature for one hour. The crystals precipitated were collected by filtration and dried at 50° C. for 15 hours in vacuo to afford the title compound [11.2 g, yield: 94.9%] as a pale yellow crystalline solid.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 30 minutes
  2. customAfter completion of the reaction
  3. customthe resulting mixture was partitioned
  4. washThe separated organic layer was washed with water twice (50 ml each)
  5. customevaporated to dryness
  6. additionSubsequently, to the obtained residue was added toluene (45 ml)
  7. temperaturethe resulting mixture was refluxed
  8. dissolutionto dissolve the residue
  9. customThe solution thus obtained
  10. temperaturewas cooled to 0-5° C. over about one hour
  11. stirringstirred at the same temperature for one hour
  12. customThe crystals precipitated
  13. filtrationwere collected by filtration
  14. customdried at 50° C. for 15 hours in vacuo

Sources & evidence

ORD record
ord-1dcff4c8cdc44c76ad4a0987591aeba2
Source dataset
uspto-grants-2009_07
Patent number
US07560549B2

Reaction notes

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