N,N,N',N'-Tetramethylethylenediamine → 7-(1-Benzyl-4-hydroxy-4-piperidinyl)-2,3-dihydro-2,2-dimethylbenzofuran

HRID 1290785Notes

Reaction equation

HRID 1290785 reaction equation
[CH3:1][C:2]1([CH3:11])[CH2:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[O:3]1.CN(C)CCN(C)C.[Li]CCCC.[CH2:25]([N:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CCCCCCC.CCCCCC>[CH2:25]([N:32]1[CH2:37][CH2:36][C:35]([C:10]2[C:4]3[O:3][C:2]([CH3:11])([CH3:1])[CH2:6][C:5]=3[CH:7]=[CH:8][CH:9]=2)([OH:38])[CH2:34][CH2:33]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 192201-Benzyl-4-piperidoneHCID 806402,3-Dihydro-2,2-dimethylbenzofuranHCID 178418339Butyllithium

Product 1

HCID 232826747-(1-Benzyl-4-hydroxy-4-piperidinyl)-2,3-dihydro-2,2-dimethylbenzofuranYield 19.3%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8900HeptaneSolvent2×

Conditions

Temperature
-40 °C

Procedure

A mixture of 2,3-dihydro-2,2-dimethylbenzofuran (25 g) and tetramethylethylenediamine (46 g) in heptane (250 ml) was treated dropwise at room temperature with 1.6M BuLi in hexane (250 ml). After stirring for 1.5 h at 30°-40° C. the mixture was cooled to -40° C. and 1-benzyl-4-piperidinone (32 g) was added dropwise at -40° C. The reaction mixture was allowed to warm to room temperature during 3 h followed by quench with water. After concentrating the reaction mixture in vacuo dichloromethane (500 ml) was added followed by wash with water (3×500 ml). Removal of solvent in vacuo gave an oil which was purified by flash chromatography (silica gel, heptane/ethyl acetate/triethylamine 50:48:2) giving an oil. Addition of heptane gave the product, 7-(1-benzyl-4-hydroxy-4-piperidinyl)-2,3-dihydro-2,2-dimethylbenzofuran as a solid (11 g).

Workup

  1. temperatureto warm to room temperature during 3 h
  2. customby quench with water
  3. concentrationAfter concentrating the reaction mixture in vacuo dichloromethane (500 ml)
  4. additionwas added
  5. washby wash with water (3×500 ml)
  6. customRemoval of solvent in vacuo
  7. customgave an oil which
  8. customwas purified by flash chromatography (silica gel, heptane/ethyl acetate/triethylamine 50:48:2)
  9. customgiving an oil

Sources & evidence

ORD record
ord-6ddc69317b1c45f3baa6568fee8abff8
Source dataset
uspto-grants-1998_05
Patent number
US05753661

Reaction notes

Loading…