Toluene → (S)-3-[(2,3-dihydro-5-methoxy-1H-inden-4-yl)oxy]-1-(phenylmethyl)-pyrrolidine

HRID 2185651Notes

Reaction equation

HRID 2185651 reaction equation
[H-].[Na+].CS([O:7][C@@H:8]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9]1)(=O)=O.S([O-])(=O)(=O)C.C1(C)C=CC=CC=1.[CH3:32][O:33][C:34]1[CH:42]=[CH:41][C:40]2[CH2:39][CH2:38][CH2:37][C:36]=2[C:35]=1O>CN(C)C=O>[CH3:32][O:33][C:34]1[C:35]([O:7][C@H:8]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:9]2)=[C:36]2[C:40](=[CH:41][CH:42]=1)[CH2:39][CH2:38][CH2:37]2

Participants

7

Reactant 5

HCID 1140TolueneHCID 24758Sodium hydrideHCID 85257MethanesulfonateHCID 110082602,3-dihydro-5-methoxy-1H-inden-4-olHCID 118072543-Pyrrolidinol, 1-(phenylmethyl)-, 3-methanesulfonate, (3R)-

Product 1

HCID 11759117(S)-3-[(2,3-dihydro-5-methoxy-1H-inden-4-yl)oxy]-1-(phenylmethyl)-pyrrolidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
100 °C

Procedure

In 540 ml of anhydrous dimethylformamide 5 g of 2,3-dihydro-5-methoxy-1H-inden-4-ol were dissolved. The solution was stirred, placed under a steam of nitrogen and 1.5 g of a 60% dispersion of sodium hydride in oil was added. The reaction mixture was stirred at room temperature for half an hour. The temperature was raised to 100° C. and a solution of 7.78 g of (R)-3-methanesulfonyloxy-1-(phenylmethyl)-pyrrolidine in 78 ml of anhydrous dimethylformamide was added dropwise over 1 hour. Another 3,0 g of mesylate in 30 ml of anhydrous dimethylformamide were added dropwise over 0.5 hours and the reaction continued for another 1.5 hours at 100° C. Evaporation in vacuo gave a semi solid that was partitioned between water and ethyl acetate. The ethyl acetate extract was dried and evaporated in vacuo. The derived product was isolated by chromatography over silica using toluene/-ethanol as the eluent giving 9.45g of (S)-3-[(2,3-dihydro-5-methoxy-1H-inden-4-yl)oxy]-1-(phenylmethyl)-pyrrolidine as an oil. M.S. (C.I.) (M/Z): 324 [M+H]+.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at room temperature for half an hour
  3. customEvaporation in vacuo
  4. customgave a semi solid
  5. customthat was partitioned between water and ethyl acetate
  6. extractionThe ethyl acetate extract
  7. customwas dried
  8. customevaporated in vacuo
  9. customThe derived product was isolated by chromatography over silica

Sources & evidence

ORD record
ord-e24818a05bc046e4886266df73964440
Source dataset
uspto-grants-2002_06
Patent number
US06403573B1

Reaction notes

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