Formaldehyde → (2S, 4S)-4-(4-methoxybenzylthio)-2-methoxycarbonyl-1-methylpyrrolidine

HRID 5094Notes

Reaction equation

HRID 5094 reaction equation
C=O.[CH3:3][O:4][C:5]1[CH:21]=[CH:20][C:8]([CH2:9][S:10][C@@H:11]2[CH2:15][NH:14][C@H:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12]2)=[CH:7][CH:6]=1.[C:22]([BH3-])#N.[Na+].[OH-].[Na+].[Cl-].[Na+]>C(#N)C.C(O)(=O)C>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:9][S:10][C@@H:11]2[CH2:15][N:14]([CH3:22])[C@H:13]([C:16]([O:18][CH3:19])=[O:17])[CH2:12]2)=[CH:20][CH:21]=1

Participants

8

Reactant 5

HCID 712FormaldehydeHCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 15200411(2S, 4S)-4-(4-Methoxybenzylthio)-2-methoxycarbonylpyrrolidine

Product 1

HCID 57321322(2S, 4S)-4-(4-methoxybenzylthio)-2-methoxycarbonyl-1-methylpyrrolidineYield 55.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent

Procedure

3.43 ml of 35% formalin were added to a solution of 2.25 g of (2S, 4S)-4-(4-methoxybenzylthio)-2-methoxycarbonylpyrrolidine dissolved in 42 ml of acetonitrile. Subsequently, 804 mg of sodium cyanoborohydride were divided into three portions and added to the mixture over a period of 5 minutes. The mixture was then stirred at room temperature for 30 minutes. At the end of this time, the mixture was cooled, 1.3 ml of acetic acid was added, and the reaction mixture was stirred at room temperature for 40 minutes. 40 ml of a 1N aqueous solution of sodium hydroxide and an aqueous solution of sodium chloride were then added to the mixture, after which it was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the residue was purified by a similar procedure to that described in Preparation 4-(10), to afford 1.31 g of the title compound as an oil. The infra-red spectrum, nuclear magnetic resonance spectrum and thin layer chromatograph of this compound were identical to those of the compound prepared as described in Preparation 4-(10).

Workup

  1. additionadded to the mixture over a period of 5 minutes
  2. temperatureAt the end of this time, the mixture was cooled
  3. stirringthe reaction mixture was stirred at room temperature for 40 minutes
  4. extractionafter which it was extracted with ethyl acetate
  5. washThe extract was washed with an aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was then removed by distillation under reduced pressure
  8. customthe residue was purified by a similar procedure to
  9. customthat described in Preparation 4-(10)

Sources & evidence

ORD record
ord-b28c3c4412f2482a9c5bfbab0040da2c
Source dataset
uspto-grants-1993_09
Patent number
US05242914

Reaction notes

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