HCID 701019, compound → HCID 86664325, compound

HRID 1039773Notes

Reaction equation

HRID 1039773 reaction equation
Cl[C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([Cl:20])[N:3]=1.[CH:21]([Mg]Cl)([CH3:23])[CH3:22]>C1COCC1>[Cl:20][C:4]1[N:3]=[C:2]([CH:21]([CH3:23])[CH3:22])[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=1

Participants

4

Reactant 2

HCID 701019HCID 701019, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 86664325HCID 86664325, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

A solution of 6.0 g (18.3 mmol) 2,6-dichloro-N-(4-chlorobenzyl)-4-methyl-pyridine-3-carboxylic acid amide (synthesized according to the method described in section a) of example 2) in THF (180 ml) and NMP (60 ml) was degassed for 30 min followed by the addition of 1.3 g (3.7 mmol) Fe(acac)3. This mixture was degassed again for 20 min. At −40° C. 137 ml (2M in THF, 274 mmol) isopropylmagnesiumchloride was added dropwise over 1 h. The reaction mixture was allowed to reach 0° C. and was quenched at this temperature with a sat. aq. NH4Cl sol. followed by stirring at 10° C. for 30 min. Then the mixture was diluted with EtOAc and the organic layer was separated, washed with water and brine, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 9:1) provided 2.45 g (7.3 mmol, 40%) 6-chloro-N-(4-chlorobenzyl)-2-isopropyl-4-methyl-pyridine-3-carboxylic amide.

Workup

  1. customNMP (60 ml) was degassed for 30 min
  2. customThis mixture was degassed again for 20 min
  3. customAt −40° C
  4. customto reach 0° C.
  5. customwas quenched at this temperature with a sat. aq. NH4Cl sol.
  6. additionThen the mixture was diluted with EtOAc
  7. customthe organic layer was separated
  8. washwashed with water and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by CC (hexane/EtOAc 9:1)

Sources & evidence

ORD record
ord-128218eab90c44a887acfeec3e07adfa
Source dataset
uspto-grants-2013_10
Patent number
US08552200B2

Reaction notes

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