Furan, 2-(bromomethyl)tetrahydro- → 1-(Ethylsulfonyl)-4-[(tetrahydro-2-furanyl)methyl]-4-piperidinecarbonitrile

HRID 551159Notes

Reaction equation

HRID 551159 reaction equation
[CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]#[N:13])[CH2:8][CH2:7]1)(=[O:5])=[O:4])[CH3:2].Br[CH2:15][CH:16]1[CH2:20][CH2:19][CH2:18][O:17]1>C1(C)C=CC=CC=1>[CH2:1]([S:3]([N:6]1[CH2:7][CH2:8][C:9]([CH2:15][CH:16]2[CH2:20][CH2:19][CH2:18][O:17]2)([C:12]#[N:13])[CH2:10][CH2:11]1)(=[O:4])=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 14501Furan, 2-(bromomethyl)tetrahydro-HCID 39240504HCID 39240504, compound

Product 1

HCID 579311911-(Ethylsulfonyl)-4-[(tetrahydro-2-furanyl)methyl]-4-piperidinecarbonitrile

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

In a dry round bottom flask was placed 1-(ethylsulfonyl)-4-ethynylpiperidine (14) (6.7 g, 33.1 mmol) and anhydrous toluene (200 ml). To this was added 2-(bromomethyl)tetrahydrofuran (6.51 ml, 49.7 mmol). Solid KHMDS1.2 equiv (7.93 g, 39.7 mmol) was added in one portion at room temperature and an exotherm was observed. The solution was allowed to stir for 12 hours at which time it was quenched with saturated aq. NH4Cl solution (100 ml). To the mixture was added EtOAc (50 ml) and the solution was then extracted by dilution with 250 ml, water and 3 washes with EtOAc (75 ml each). The organic layer was washed with brine (200 ml) and dried over MgSO4. The organic solvent was removed in vacuo to give a yellow solid. The residue was purified by column chromatography on silica gel, eluting with EtOAc/Hexanes to give 1-(ethylsulfonyl)-4-(tetrahydrofuran-2-ylmethyl)piperidine-4-carbonitrile (15) as a off-white solid. MS 287 (M+1)

Workup

  1. customIn a dry round bottom flask was placed
  2. addition2 equiv (7.93 g, 39.7 mmol) was added in one portion at room temperature
  3. customwas quenched with saturated aq. NH4Cl solution (100 ml)
  4. additionTo the mixture was added EtOAc (50 ml)
  5. extractionthe solution was then extracted by dilution with 250 ml, water and 3
  6. washThe organic layer was washed with brine (200 ml)
  7. dry with materialdried over MgSO4
  8. customThe organic solvent was removed in vacuo
  9. customto give a yellow solid
  10. customThe residue was purified by column chromatography on silica gel
  11. washeluting with EtOAc/Hexanes

Sources & evidence

ORD record
ord-3f791c5bc65d4f0393395454e7b5ded5
Source dataset
uspto-grants-2011_05
Patent number
US07947714B2

Reaction notes

Loading…