Diisopropylethylamine → 2,3-Dichloro-4-(4-fluoro-4-phenylpiperidin-1-yl)pyridine

HRID 587633Notes

Reaction equation

HRID 587633 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6](I)[CH:5]=[CH:4][N:3]=1.Cl.[F:11][C:12]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CC#N>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([N:15]2[CH2:16][CH2:17][C:12]([F:11])([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:13][CH2:14]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 448870382,3-Dichloro-4-iodopyridineHCID 459337594-Fluoro-4-phenylpiperidine hydrochloride

Product 1

HCID 574595992,3-Dichloro-4-(4-fluoro-4-phenylpiperidin-1-yl)pyridine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of D10 (2 g, 7.302 mmol), 4-fluoro-4-phenylpiperidine hydrochloride (2.048 g, 9.493 mmol) [C.A.S. 1056382-25-2] and DIPEA (5.055 ml, 29.209 mmol) in CH3CN (10 ml) was heated in a sealed tube at 110° C. for 16 h. The mixture was then treated with NaHCO3 (aqueous sat. solution). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; Heptane/DCM from 4:1 up to 1:4 as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D18 (0.88 g, 37%) as a white solid.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by column chromatography (silica gel; Heptane/DCM from 4:1 up to 1:4 as eluent)
  5. customThe desired fractions were collected
  6. concentrationconcentrated in vacuo
  7. customto yield intermediate compound

Sources & evidence

ORD record
ord-1a905621b0224dcabcf1ade3d87e35f3
Source dataset
uspto-grants-2016_01
Patent number
US09226930B2

Reaction notes

Loading…