Triethylamine → (R)-3-methanesulfonyloxy-1-(3-pyrrolidinophenethyl)pyrrolidine

HRID 2251898Notes

Reaction equation

HRID 2251898 reaction equation
S(O[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[CH:9]=1)(=O)(=O)C.Cl.[NH:20]1[CH2:24][CH2:23][C@H:22]([OH:25])[CH2:21]1.C(=O)([O-])[O-].[K+].[K+].C(N(CC)CC)C.[CH3:39][S:40](Cl)(=[O:42])=[O:41].C(=O)([O-])O.[Na+]>ClCCl.C(#N)C>[CH3:39][S:40]([O:25][C@@H:22]1[CH2:23][CH2:24][N:20]([CH2:6][CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([N:14]3[CH2:15][CH2:16][CH2:17][CH2:18]3)[CH:9]=2)[CH2:21]1)(=[O:42])=[O:41]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 22309122(S)-3-Hydroxypyrrolidine hydrochlorideHCID 22934159HCID 22934159, compound

Product 1

HCID 86592730(R)-3-methanesulfonyloxy-1-(3-pyrrolidinophenethyl)pyrrolidine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

3-Pyrrolidinophenethyl mesylate (1.80 g, 4.00 mmol), (S)-3-pyrrolidinol hydrochloride (0.50 g, 4.05 mmol) and potassium carbonate (1.70 g, 12.3 mmol) were added to acetonitrile (20 ml), and they were stirred at 100° C. for 12 hours. Acetonitrile was evaporated under reduced pressure, and the residue was distributed into water and ethyl acetate. The intended product was extracted from the ethyl acetate layer with 1 M hydrochloric acid. After neutralizing the aqueous layer, the product was again extracted with ethyl acetate. The organic layer was dried and then the solvent was evaporated under reduced pressure to quantitatively obtain (S)-3-hydroxy-1-(3-pyrrolidinophenethyl)pyrrolidine in the form of a light yellow solid. This product was dissolved in dichloromethane (10 ml). Triethylamine (0.76 ml, 5.49 mmol) and methanesulfonyl chloride (0.39 ml, 5.03 mmol) were added to the obtained solution at 0° C. and they were stirred overnight. The reaction mixture was distributed into 5% aqueous sodium hydrogencarbonate solution and dichloromethane. The organic layer was dried and then the solvent was evaporated under reduced pressure. The residue was subjected to the silica gel column chromatography. After the elution with chloroform and methanol (95:5), suitable fractions were collected and the solvent was evaporated under reduced pressure to obtain (R)-3-methanesulfonyloxy-1-(3-pyrrolidinophenethyl)pyrrolidine in the form of a light yellow oily substance (1.30 g, 96%).

Workup

  1. customAcetonitrile was evaporated under reduced pressure
  2. extractionThe intended product was extracted from the ethyl acetate layer with 1 M hydrochloric acid
  3. extractionthe product was again extracted with ethyl acetate
  4. customThe organic layer was dried
  5. customthe solvent was evaporated under reduced pressure to quantitatively obtain (S)-3-hydroxy-1-(3-pyrrolidinophenethyl)pyrrolidine in the form of a light yellow solid
  6. dissolutionThis product was dissolved in dichloromethane (10 ml)
  7. stirringthey were stirred overnight
  8. customThe organic layer was dried
  9. customthe solvent was evaporated under reduced pressure
  10. washAfter the elution with chloroform and methanol (95:5), suitable fractions
  11. customwere collected
  12. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-e5c6fa58403447efa564aa51242579a1
Source dataset
uspto-grants-2008_01
Patent number
US07320973B2

Reaction notes

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