Hexane → 4-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]-1-methyl-4-piperidinol

HRID 2216374

Reaction equation

HRID 2216374 reaction equation
[CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCCCCC.C([Li])CCC.[CH3:34][N:35]1[CH2:40][CH2:39][C:38](=[O:41])[CH2:37][CH2:36]1>C(OCC)C>[CH2:1]([C:8]1[C:13]([C:38]2([OH:41])[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 740491-Methyl-4-piperidoneHCID 113843072-Benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridineHCID 178418339Butyllithium

Product 1

HCID 587007554-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]-1-methyl-4-piperidinolYield 25.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a mixture of 500 mg of 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridine (Production Example 1) and 10 ml of diethyl ether was added dropwise 1.99 ml of a 2.45 M hexane solution of n-butyllithium at −78° C. After stirring at the same temperature for 30 minutes, a solution of 552 mg of 1-methyl-4-piperidone in 3 ml of diethyl ether was added dropwise thereto. After stirring at the same temperature for 30 minutes, the temperature was elevated to room temperature. The organic layer was separated by adding water and ethyl acetate to the reaction mixture, and then it was washed with water and brine, dried over anhydrous magnesium sulfate and the solvent was removed. The residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate, to give 125 mg of the title compound.

Workup

  1. stirringAfter stirring at the same temperature for 30 minutes
  2. customwas elevated to room temperature
  3. customThe organic layer was separated
  4. additionby adding water and ethyl acetate to the reaction mixture
  5. washit was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was removed
  8. customThe residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-85f3a0ea4d0842cc86bc3566a4b7d3a1
Source dataset
uspto-grants-2006_09
Patent number
US07112593B2

Linked notes

Loading…