4-Chlorobenzenesulfonyl chloride → (2R)-2-[2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl 4-chlorobenzenesulfonate

HRID 227543Notes

Reaction equation

HRID 227543 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.[Cl:49][C:50]1[CH:55]=[CH:54][C:53]([S:56](Cl)(=[O:58])=[O:57])=[CH:52][CH:51]=1.CC1CCCCC1>C(Cl)Cl.C1(C)C=CC=CC=1.O>[Cl:49][C:50]1[CH:55]=[CH:54][C:53]([S:56]([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:58])=[O:57])=[CH:52][CH:51]=1

Participants

10

Reactant 6

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 7962MethylcyclohexaneHCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 10956756(2R)-2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol

Product 1

HCID 11204501(2R)-2-[2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethyl 4-chlorobenzenesulfonateYield 95.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
2.5 °C

Procedure

To a mixture of (2R)-2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol (3.0 g, 10.9 mmol) and methylene chloride (30 ml), triethylamine (4.5 ml, 32.6 mmol) was added under a nitrogen stream, the resulting mixture was cooled to 0-5° C., and then a solution of 3,4,5-trimethoxybenzoyl chloride (2.6 g, 11.1 mmol) in methylene chloride (12 ml) was further added dropwise at below 10° C. After the reaction mixture was stirred at 0-5° C. for 30 minutes, dimethylaminopyridine (0.13 g, 1.1 mmol) was added at the same temperature. Subsequently, to the resulting mixture was added dropwise a solution of 4-chlorobenzenesulfonyl chloride (3.4 g, 16.3 mmol) in methylene chloride (12 ml) at below 10° C., and the resulting mixture was stirred at 0-5° C. for 4 hours. After completion of the reaction, to the reaction mixture was added water (30 ml), and the resulting mixture was partitioned. The separated organic layer was washed successively with 1N hydrochloric acid (30 ml), a 5% aqueous solution of sodium hydrogencarbonate (30 ml) and water (30 ml) and evaporated to dryness. Subsequently, to the residue obtained was added toluene to make the total volume 18 ml, and the resulting mixture was heated at 40° C. Furthermore, to the solution obtained was added methylcyclohexane (9 ml), and the resulting mixture was stirred at 40° C. for 30 minutes, and then at 0-5° C. for 30 minutes. The crystals precipitated were collected by filtration and dried at 50° C. in vacuo to afford the title compound [6.7 g, yield: 95.6%] as a pale yellow crystalline compound.

Workup

  1. additionwas added under a nitrogen stream
  2. stirringthe resulting mixture was stirred at 0-5° C. for 4 hours
  3. customAfter completion of the reaction
  4. customthe resulting mixture was partitioned
  5. washThe separated organic layer was washed successively with 1N hydrochloric acid (30 ml)
  6. customa 5% aqueous solution of sodium hydrogencarbonate (30 ml) and water (30 ml) and evaporated to dryness
  7. customSubsequently, to the residue obtained
  8. temperaturethe resulting mixture was heated at 40° C
  9. customFurthermore, to the solution obtained
  10. stirringthe resulting mixture was stirred at 40° C. for 30 minutes
  11. waitat 0-5° C. for 30 minutes
  12. customThe crystals precipitated
  13. filtrationwere collected by filtration
  14. customdried at 50° C. in vacuo

Sources & evidence

ORD record
ord-b2e6370926a448059700f22a853fa5d0
Source dataset
uspto-grants-2009_07
Patent number
US07560549B2

Reaction notes

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