Acetonitrile → 1'-(2,3-Dichloropyridin-4-yl)spiro[1-benzofuran-3,4'-piperidine]

HRID 587639Notes

Reaction equation

HRID 587639 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6](I)[CH:5]=[CH:4][N:3]=1.CC[N:12]([CH:16]([CH3:18])C)[CH:13]([CH3:15])C.[C:19]([O-:22])(O)=O.[Na+].[CH3:24][C:25]#N>>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([N:12]2[CH2:13][CH2:15][C:7]3([C:6]4[CH:5]=[CH:4][CH:25]=[CH:24][C:19]=4[O:22][CH2:2]3)[CH2:18][CH2:16]2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 448870382,3-Dichloro-4-iodopyridine

Product 1

HCID 866679871'-(2,3-Dichloropyridin-4-yl)spiro[1-benzofuran-3,4'-piperidine]

Conditions

Temperature
110 °C

Procedure

A mixture of intermediate D10 (3 g, 10.953 mmol), 4-spiro-[3-(2,3-dihydro-benzofuran)]piperidine [CAS 171-77-7] (2.28 g, 12.049 mmol and DIPEA (7.63 ml, 43.814 mmol) in CH3CN (100 ml) was heated in a sealed tube at 110° C. for 3 days. The mixture was then treated with NaHCO3 (aqueous sat. solution) and extracted with EtOAc. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 4% as eluent), the desired fractions were collected and concentrated in vacuo to yield intermediate D48 (2.9 g, 63%) as a white solid. M.P. 177.2° C.

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 4% as eluent)
  6. customthe desired fractions were collected
  7. concentrationconcentrated in vacuo
  8. customto yield intermediate D48 (2.9 g, 63%) as a white solid

Sources & evidence

ORD record
ord-84dac9c229f744eba560e1539528c25d
Source dataset
uspto-grants-2016_01
Patent number
US09226930B2

Reaction notes

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