4-Toluenesulfonyl chloride → 5-benzylhexahydro-1H-furo[3,4-c]pyrrole

HRID 712438Notes

Reaction equation

HRID 712438 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.CCN(CC)CC.S(Cl)(C1C=CC(C)=CC=1)(=O)=O>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C>[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

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 13814311[1-Benzyl-4-(hydroxymethyl)pyrrolidin-3-yl]methanol

Product 1

HCID 215185425-benzylhexahydro-1H-furo[3,4-c]pyrroleYield 62.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent

Procedure

To a solution of (1-benzylpyrrolidine-3,4-diyl)dimethanol (1.44 g) in toluene (60 mL) was added Et3N (1.72 mL), TsCl (1.75 g) and DMAP (40 mg). The reaction mixture was stirred at room temperature for 12 h under N2, washed with water once, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was used for next step. To a solution of the above product in toluene (20 mL) was added Et3N (0.85 mL). The reaction mixture was heated to reflux for 4 h and cooled to room temperature. The reaction mixture was washed with water followed by brine, dried over anhydrous Na2SO4 and filtrated. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to afford the title compound (0.51 g, 62.30%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 204.3 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.31-2.35 (m, 2H), 2.71 (m, 2H), 2.79-2.81 (m, 2H), 3.57-3.60 (m, 4H), 3.76-3.80 (m, 2H), 7.24-7.34 (m, 5H) ppm.

Workup

  1. washwashed with water once
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. additionTo a solution of the above product in toluene (20 mL) was added Et3N (0.85 mL)
  6. temperatureThe reaction mixture was heated
  7. temperatureto reflux for 4 h
  8. temperaturecooled to room temperature
  9. washThe reaction mixture was washed with water
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltrated
  12. concentrationThe filtrate was concentrated in vacuo
  13. customthe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH)

Sources & evidence

ORD record
ord-84a021a5f8d24a12abadd9822b60912d
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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