Ammonium Chloride → 3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

HRID 1617505Notes

Reaction equation

[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([CH3:13])[CH:8]=1.[Br:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[CH2:22][C:23](N(OC)C)=[O:24])=[CH:17][CH:16]=1.[NH4+].[Cl-]>C1COCC1>[Br:14][C:15]1[CH:16]=[CH:17][C:18]([CH:21]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[CH2:22][C:23]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([CH3:13])[CH:8]=2)=[O:24])=[CH:19][CH:20]=1

Participants

Conditions

Temperature: -70 °C

Procedure

To a solution of n-BuLi (12.9 mL 1.6 M in hexane) was added dropwise a solution of 4-bromo-2-methylpyridine (3.56 g) in THF (170 mL) at −70° C. over a period of 20 min. The reaction mixture was stirred at −70° C. for 5 min, before a solution of 3-(4-bromo-phenyl)-N-methoxy-N-methyl-3-o-tolyl-propionamide (2.5 g) in THF (100 mL) was added dropwise. After the addition was complete, the mixture was stirred at −70° C. for 3 hours. A saturated 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 1:1) to give the title compound as an yellow oil (1.49 g, 55%), MS (ESI+): m/z=394.0797 ([M+H]+, 1Br).

Workup

additionwas added dropwise
additionAfter the addition
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 1:1)

Sources & evidence

ORD record: ord-a3dccd2b4ee94ae2be82da43bba1a661
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765730B2

Reaction notes

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