Dimethylformamide → HCID 17974702, compound

HRID 2202688Notes

Reaction equation

HRID 2202688 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[Cl:12].C([Li])CCC.CN([CH:21]=[O:22])C>C1COCC1>[Cl:12][C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[CH:21]=[O:22])=[CH:10][CH:9]=[CH:8][CH:7]=2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 459257434-Bromo-3-chloroquinolineHCID 178418339Butyllithium

Product 1

HCID 17974702HCID 17974702, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A flask was charged with 4-bromo-3-chloroquinoline (A275-2) (1.00 g, 4.12 mmol) and THF (16.5 mL) under nitrogen, and the solution was cooled to −78° C. To the cooled mixture was added n-butyllithium (2.5 M solution in hexane, 1.65 mL, 4.12 mmol) and the mixture was stirred at −78° C. for 1 hour. To the mixture was added DMF (1.60 mL, 20.6 mmol) dropwise, and the mixture was allowed to warm to room temperature. After 4 h, the mixture was quenched with saturated aqueous NH4Cl (20 mL). The mixture was partitioned between water (50 mL) and EtOAc (50 mL). The aqueous layer was extracted with EtOAc (1×50 mL). The organic extract was dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude material as a brown syrup. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a REDISEP™ pre-packed silica gel column (80 g), eluting with a gradient of 0% to 20% EtOAc in hexane, and dried under high vacuum to give 3-chloroquinoline-4-carbaldehyde (A275-3) as brown solid. 1H NMR (400 MHz, DMSO-d6) δ 10.74 (1H, s), 9.10 (1H, s), 8.68-8.73 (1H, m), 8.15 (1H, dd, J=8.5, 0.9 Hz), 7.79-7.92 (2H, m); LCMS (ESI) m/z 192.1 (M+H)+.

Workup

  1. temperatureto warm to room temperature
  2. waitAfter 4 h
  3. customthe mixture was quenched with saturated aqueous NH4Cl (20 mL)
  4. customThe mixture was partitioned between water (50 mL) and EtOAc (50 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (1×50 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried over MgSO4
  8. filtrationThe solution was filtered
  9. concentrationconcentrated in vacuo
  10. customto give the crude material as a brown syrup
  11. customThe crude material was absorbed onto a plug of silica gel
  12. custompurified by chromatography through a REDISEP™ pre-packed silica gel column (80 g)
  13. washeluting with a gradient of 0% to 20% EtOAc in hexane
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-68f7578b0b6b41ff9eb8fa46bdee3f8a
Source dataset
uspto-grants-2016_06
Patent number
US09365522B2

Reaction notes

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