Ammonium Chloride → 1-(2,6-Dichloro-pyridin-4-yl)-3,3-diphenyl-propan-1-one

HRID 1617501Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([Cl:9])[N:3]=1.[Li]CCCC.CON(C)[C:18](=[O:33])[CH2:19][CH:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[NH4+].[Cl-]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:18](=[O:33])[CH2:19][CH:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:5]=[C:4]([Cl:9])[N:3]=1

Participants

Conditions

Temperature: -70 °C

Procedure

At −70° C. to a solution of 2,6-dichloro-4-iodopyridine (1.02 g) in THF (20 mL) was added n-BuLi (1.6 M in hexane, 2.3 mL) dropwise. The mixture was stirred for additional 15 min at which timepoint a solution of N-methoxy-N-methyl-3,3-diphenyl-propionamide (200 mg) in THF (10 mL) was added. The reaction mixture was stirred for 1 hour at −70° C. A saturated aqueous solution of NH4Cl was added, the phases were separated and the inorganic one was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 1:10) to yield 1-(2,6-dichloro-pyridin-4-yl)-3,3-diphenyl-propan-1-one (465 mg, 88%) as a yellow oil, which was directly subjected to the next step.

Workup

additionwas added
customthe phases were separated
extractionthe inorganic one was extracted with EtOAc (2×)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography on silica gel (EtOAc/n-heptane 1:10)

Sources & evidence

ORD record: ord-b3d1d2c0ff1142c390329dbfa54dc81d
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765730B2

Reaction notes

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