Triethylamine → (S)-N-[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]-N-ethyl-(1-chlorosulfonylpiperidin-4-ylmethyl)amine

HRID 429839Notes

Reaction equation

HRID 429839 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][C@@H:11]([N:13]([CH2:16][CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH2:14][CH3:15])[CH3:12])=[CH:9][C:4]=2[CH2:3][CH2:2]1.C(N(CC)CC)C.[Cl:30][S:31](O)(=[O:33])=[O:32].P(Cl)(Cl)(Cl)(Cl)Cl>ClCCl.C1C=CC=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][C@@H:11]([N:13]([CH2:16][CH:17]3[CH2:22][CH2:21][N:20]([S:31]([Cl:30])(=[O:33])=[O:32])[CH2:19][CH2:18]3)[CH2:14][CH3:15])[CH3:12])=[CH:9][C:4]=2[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24638Chlorosulfonic acidHCID 24819Phosphorus pentachlorideHCID 15546287(S)-N-[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]-N-ethyl-(piperidin-4-ylmethyl)amine

Product 1

HCID 53697435(S)-N-[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]-N-ethyl-(1-chlorosulfonylpiperidin-4-ylmethyl)amineYield 70%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-N-[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]-N-ethyl-(piperidin-4-ylmethyl)amine (0.2 grams, 0.66 mmole) and triethylamine (0.15 grams, 1.48 mmole) in dichloromethane (4 ml) at 0° C. was added dropwise a solution of chlorosulfonic acid (0.08 grams, 0.66 mmol) in dichloromethane (0.5 ml). The mixture was stirred at room temperature for 16 hours, and the solvent was removed under reduced pressure. To the residue was added benzene (4 ml) and phosphorous pentachloride (0.14 grams, 0.67 mmole). The mixture was heated under reflux for 2 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and 1N sodium hydroxide. The organic layer was washed with brine, dried over sodium sulfate and concentrated to give (S)-N-[2-(2,3-dihydrobenzofuran-5-yl)-1-methylethyl]-N-ethyl-(1-chlorosulfonylpiperidin-4-ylmethyl)amine as a viscous oil (0.18 grams, 70%), M+H 401.

Workup

  1. customthe solvent was removed under reduced pressure
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 2 hours
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was partitioned between ethyl acetate and 1N sodium hydroxide
  6. washThe organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-dd0cecd1dbb84b35b6abbe9207d2f810
Source dataset
uspto-grants-2001_11
Patent number
US06319920B1

Reaction notes

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