Dimethylformamide → HCID 86716090, compound

HRID 627524Notes

Reaction equation

HRID 627524 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=1)[N:13]=[C:12]([Cl:18])[C:11]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[C:10]2[Cl:25].CN([CH:29]=[O:30])C>C1COCC1>[Cl:18][C:12]1[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:10]([Cl:25])[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]([CH:29]=[O:30])[CH:8]=2)[N:13]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 86716089HCID 86716089, compoundHCID 178418339Butyllithium

Product 1

HCID 86716090HCID 86716090, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-72 °C

Procedure

A −71° C. solution of n-BuLi (6.14 mL, 1.59 M in hexane, 9.77 mmol) under argon was treated with a solution of 6-bromo-2,4-dichloro-8-methyl-3-phenylquinoline (3.26 g, 8.81 mmol, Intermediate 47, step a) in THF (27 mL) as an intermittent fine stream over 28 min. After a few minutes, DMF (1.38 mL, 17.8 mmol) was added dropwise over 2 min to the reddish-brown reaction, and the resulting greenish-black mixture was stirred at −72° C. for 30 min. The reaction was removed from the cold bath and allowed to stir under ambient conditions for 10 min, and was then quenched in one portion with 5 M NH4Cl (7 mL), partitioned with 4:1 EtOAc/heptane (50 mL) and 5:3 4 M NaCl/5 M NaBr (40 mL), and filtered. The filter cake was dissolved in 9:1 DCM/MeOH (15 mL), and this was combined with the clear yellow organic layer filtrate and dried (Na2SO4), filtered, and concentrated. The residue was dry load flash chromatographed with a 20% DCM/heptane to 100% DCM gradient to afford the title compound as a white solid.

Workup

  1. waitAfter a few minutes
  2. customThe reaction was removed from the cold bath
  3. stirringto stir under ambient conditions for 10 min
  4. customwas then quenched in one portion with 5 M NH4Cl (7 mL)
  5. custompartitioned with 4:1 EtOAc/heptane (50 mL) and 5:3 4 M NaCl/5 M NaBr (40 mL)
  6. filtrationfiltered
  7. dissolutionThe filter cake was dissolved in 9:1 DCM/MeOH (15 mL)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was dry load flash
  12. customchromatographed with a 20% DCM/heptane to 100% DCM gradient

Sources & evidence

ORD record
ord-f9fae7635a064064b77ac33b59a09b1b
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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