Methyl 3-[4-(3-Benzyloxyphenyl)-4-fluoropiperidin-1-yl]propionate → 3-[4-(3-Benzyloxyphenyl)-4-fluoropiperidin-1-yl]-1,1-dibenzylpropan-1-ol

HRID 537213Notes

Reaction equation

HRID 537213 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2([F:27])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][C:23]([O:25]C)=O)[CH2:17][CH2:16]2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28]([Mg]Cl)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:15]2([F:27])[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][C:23]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[OH:25])[CH2:17][CH2:16]2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 67466200Methyl 3-[4-(3-Benzyloxyphenyl)-4-fluoropiperidin-1-yl]propionateHCID 178418336HCID 178418336, compound

Product 1

HCID 674654863-[4-(3-Benzyloxyphenyl)-4-fluoropiperidin-1-yl]-1,1-dibenzylpropan-1-olYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl 3-[4-(3-benzyloxyphenyl)-4-fluoropiperidin-1-yl]propionate (100 mg, 0.27 mmol) in THF (5 mL) was cooled in an ice bath and a 2M solution of benzylmagnesium chloride in THF (0.338 mL, 0.68 mmol) added dropwise over 5 minutes. The resulting yellow solution was then stirred for 14 h during which time the reaction reached room temperature. The mixture was then quenched with 25% aqueous ammonium chloride solution (10 mL) and diluted with ethyl acetate (3×10 mL). The organic layers were then combined and dried over magnesium sulfate. Subsequent filtration, concentration and purification by silica gel chromatography (SiO2, 50% ethyl acetate/heptanes) afforded 3-[4-(3-benzyloxyphenyl)-4-fluoropiperidin-1-yl]-1,1-dibenzylpropan-1-ol as a clear viscous oil in 49% yield.

Workup

  1. customreached room temperature
  2. customThe mixture was then quenched with 25% aqueous ammonium chloride solution (10 mL)
  3. additiondiluted with ethyl acetate (3×10 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationSubsequent filtration, concentration and purification by silica gel chromatography (SiO2, 50% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-1b22e1bdb867404fab6503d2ba9823f0
Source dataset
uspto-grants-2014_10
Patent number
US08859777B2

Reaction notes

Loading…