1,2-Dichloroethane → HCID 68310473, compound

HRID 1021281Notes

Reaction equation

HRID 1021281 reaction equation
[Si]([O:8][CH2:9][C:10]1[C:11]([F:28])=[C:12]([N:16]2[CH2:21][CH2:20][CH:19]([CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[CH2:18][CH2:17]2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.ClCCCl.[C:33](Cl)(=[O:35])[CH3:34].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[F:28][C:11]1[C:10]([CH2:9][OH:8])=[CH:15][CH:14]=[CH:13][C:12]=1[N:16]1[CH2:17][CH2:18][CH:19]([CH:22]2[CH2:27][CH2:26][N:25]([C:33](=[O:35])[CH3:34])[CH2:24][CH2:23]2)[CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 6367Acetyl chlorideHCID 516892Sodium BicarbonateHCID 86686232HCID 86686232, compound

Product 1

HCID 68310473HCID 68310473, compoundYield 81.7%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

1-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-4,4′-bipiperidine (125 mg) and TEA (0.15 ml) were mixed with DCE (3 ml), and acetyl chloride (39 mg) was added thereto, followed by stirring at room temperature for 1 hour. A saturated aqueous sodium hydrogen carbonate solution and CHCl3 were added to the reaction mixture, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was mixed with THF (3 ml), and a 1 M TBAF/THF solution (0.6 ml) was added thereto, followed by stirring at room temperature for 1 hour. To the reaction mixture were added an aqueous ammonium chloride solution and EtOAc, the organic layer was dried over Na2SO4, and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain 1-{1′-[2-fluoro-3-(hydroxymethyl)phenyl]-4,4′-bipiperidin-1-yl}ethanone (84 mg).

Workup

  1. additionwas added
  2. dry with materialthe organic layer was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. additionThe obtained residue was mixed with THF (3 ml)
  5. additiona 1 M TBAF/THF solution (0.6 ml) was added
  6. stirringby stirring at room temperature for 1 hour
  7. additionTo the reaction mixture were added an aqueous ammonium chloride solution and EtOAc
  8. dry with materialthe organic layer was dried over Na2SO4
  9. concentrationthe solvent was concentrated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-6372d68bfa804b6d951fade468202f0b
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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