N,N-Dimethylaniline → (Z)-methyl 3-bromo-6-((2-(3-(diethylamino)prop-1-enyl)-4-fluorobenzenesulfonyl)methyl)-2-hydroxybenzoate

HRID 1778386Notes

Reaction equation

HRID 1778386 reaction equation
[Br:1][C:2]1[C:3]([O:31]C)=[C:4]([C:9]([CH2:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2/[CH:23]=[CH:24]\[CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])(=[O:15])=[O:14])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].CN(C)C1C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[Br:1][C:2]1[C:3]([OH:31])=[C:4]([C:9]([CH2:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2/[CH:23]=[CH:24]\[CH2:25][N:26]([CH2:27][CH3:28])[CH2:29][CH3:30])(=[O:14])=[O:15])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 949N,N-DimethylanilineHCID 6451240Aluminum(III) ChlorideHCID 66693679methyl 3-bromo-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-2-methoxybenzoate2×

Product 1

HCID 66693503(Z)-methyl 3-bromo-6-((2-(3-(diethylamino)prop-1-enyl)-4-fluorobenzenesulfonyl)methyl)-2-hydroxybenzoateYield 66.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 3-bromo-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-2-methoxybenzoate (Intermediate 69, 3.9 g) and N,N-dimethylaniline (9.00 g) in DCM (150 mL) was cooled to 0° C. and aluminium chloride (3.00 g) was added in three portions. The resultant mixture was stirred at room temperature for 2 hours. The mixture was cooled in an ice bath and quenched with brine. The layers were separated and the organic phase was dried (MgSO4), filtered and the filtrate was concentrated in vacuo. Cyclohexane was added to the residual gum and then decanted off. The residual oil was dissolved in DCM and concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-15% to give methyl 3-bromo-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylmethyl]-2-hydroxybenzoate (2.52 g) as a blue glass.

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. customquenched with brine
  3. customThe layers were separated
  4. dry with materialthe organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. additionCyclohexane was added to the residual gum
  8. customdecanted off
  9. dissolutionThe residual oil was dissolved in DCM
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by chromatography on silica
  12. washeluting with a mixture of 2M ammonia in methanol and DCM, with a gradient of 0-15%

Sources & evidence

ORD record
ord-f9964059494d41b48ab108c20de0c953
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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