Hydrochloric Acid → 2-[3-(3,4-Dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)piperidin-3-yl]ethyl 4-chlorobenzenesulfonate

HRID 227550Notes

Reaction equation

HRID 227550 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:15][CH2:16][OH:17])[CH2:14][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].[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([S:47](Cl)(=[O:49])=[O:48])=[CH:43][CH:42]=1.Cl>O1CCCC1.CN(C)C1C=CN=CC=1.C(Cl)Cl.O>[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([S:47]([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)[CH2:14][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:49])=[O:48])=[CH:43][CH:42]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 73984-Chlorobenzenesulfonyl chlorideHCID 8471Triethylamine2×HCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 154604002-[3-(3,4-Dichlorophenyl)piperidin-3-yl]ethanol

Product 1

HCID 111580092-[3-(3,4-Dichlorophenyl)-1-(3,4,5-trimethoxybenzoyl)piperidin-3-yl]ethyl 4-chlorobenzenesulfonateYield 76.3%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a solution of (+)-2-[3-(3,4-dichlorophenyl)piperidin-3-yl]ethanol (1.70 g, 6.20 mmol) in tetrahydrofuran (85 ml) was added triethylamine (1.30 ml, 9.35 mmol), and the resulting mixture was cooled to 0-5° C. After cooling, a solution of 3,4,5-trimethoxybenzoyl chloride (1.46 g, 6.33 mmol) in tetrahydrofuran (7 ml) was further added dropwise at below 5° C., and the resulting mixture was stirred at 0-5° C. for 5 hours and then evaporated to dryness in vacuo. Subsequently, to the residue obtained were added methylene chloride (50 ml), triethylamine (1.30 ml, 9.35 mmol) and 4-dimethylaminopyridine (0.076 g, 0.62 mmol), and the resulting mixture was cooled to 0-5° C. After cooling, a solution of 4-chlorobenzenesulfonyl chloride (1.57 g, 7.44 mmol) in methylene chloride (3.5 ml) was further added dropwise at below 5° C., and the resulting mixture was stirred at 0-5° C. for 5 hours. After completion of the reaction, water (50 ml) and concentrated hydrochloric acid (2 ml) were added to the reaction mixture, and the resulting mixture was partitioned. The separated organic layer was washed with water (50 ml) and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column and then crystallized from a mixed solvent of ethyl acetate (6.6 ml) and hexane (17.7 ml) under ice-cooling to afford the title compound [3.0 g, yield: 76.3%] as a colorless crystalline solid.

Workup

  1. temperatureAfter cooling
  2. customevaporated to dryness in vacuo
  3. customSubsequently, to the residue obtained
  4. temperaturethe resulting mixture was cooled to 0-5° C
  5. temperatureAfter cooling
  6. stirringthe resulting mixture was stirred at 0-5° C. for 5 hours
  7. additionwere added to the reaction mixture
  8. customthe resulting mixture was partitioned
  9. washThe separated organic layer was washed with water (50 ml)
  10. customevaporated in vacuo
  11. customThe residue obtained
  12. customwas purified by chromatography on a silica gel column
  13. customcrystallized from a mixed solvent of ethyl acetate (6.6 ml) and hexane (17.7 ml) under ice-
  14. temperaturecooling

Sources & evidence

ORD record
ord-90b4d41b485d468dadfdeaf19bfb40e9
Source dataset
uspto-grants-2009_07
Patent number
US07560549B2

Reaction notes

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