Sodium Hydroxide → 5-benzylhexahydro-1H-furo[3,4-c]pyrrole

HRID 1947454Notes

Reaction equation

HRID 1947454 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([CH2:13]O)[CH:10]([CH2:15][OH:16])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:9][CH:10]2[CH2:15][O:16][CH2:13][CH:11]2[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 521998p-Toluenesulfonic acid monohydrateHCID 13814311[1-Benzyl-4-(hydroxymethyl)pyrrolidin-3-yl]methanol

Product 1

HCID 215185425-benzylhexahydro-1H-furo[3,4-c]pyrroleYield 80.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of (1-benzyl-4-hydroxymethyl-pyrrolidin-3-yl)-methanol (7.89 g, 31.2 mmol) and p-toluenesulfonic acid monohydrate (7.12 g, 37.4 mmol) in toluene (150 mL) was heated under a Dean Stark trap (120° C., 20 h). The reaction mixture was cooled (rt) and treated with 1 N NaOH (50 mL). The aqueous phase was extracted with methyl tert-butyl ether (3×50 mL). The combined organic layers were dried, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography using MeOH (0.2 M NH3):DCM (0-5%) to afford the title compound as a yellow oil (5.08 g, 80%). 1H NMR (500 MHz, CDCl3): 7.37-7.29 (m, 4H), 7.29-7.24 (m, 1H), 3.87-3.79 (m, 2H), 3.65-3.56 (m, 4H), 2.86-2.75 (m, 2H), 2.75-2.66 (m, 2H), 2.34 (dt, J=12.2, 6.1, 2H).

Workup

  1. extractionThe aqueous phase was extracted with methyl tert-butyl ether (3×50 mL)
  2. customThe combined organic layers were dried
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7f24ddc339b24ce0a85d253fbde165d0
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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