Cesium carbonate → 2-Chloro-6-(cyclopropylmethoxy)quinoline-3-carbaldehyde

HRID 1620304Notes

Reaction equation

HRID 1620304 reaction equation
[Cl:1][C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:14])[CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:22][CH:23]1[CH2:25][CH2:24]1>CN(C=O)C>[Cl:1][C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:14][CH2:22][CH:23]3[CH2:25][CH2:24]3)[CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 210510652-Chloro-6-hydroxyquinoline-3-carbaldehyde2×

Product 1

HCID 866698362-Chloro-6-(cyclopropylmethoxy)quinoline-3-carbaldehydeYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-chloro-6-hydroxyquinoline-3-carbaldehyde SLA 47016 (1.00 g, 4.8 mmol), cesium carbonate (3.14 g, 9.6 mmol) and (bromomethyl)cyclopropane (0.94 mL, 9.6 mmol) in dry DMF (30 mL) in a 50 mL round-bottomed flask equipped with a magnetic stirrer was stirred overnight at RT. DMF was removed at 40° C. under vacuum and the residue was taken up in CH2Cl2 (50 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 95:5) followed by a new purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5) gave 2-chloro-6-(cyclopropylmethoxy)quinoline-3-carbaldehyde SLA 47086 as a pale brown solid (513 mg, 41% yield).

Workup

  1. customequipped with a magnetic stirrer
  2. customDMF was removed at 40° C. under vacuum
  3. washwashed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 95:5)
  8. customfollowed by a new purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5)

Sources & evidence

ORD record
ord-5e5f5f517e804aa3b9fe80638ef8d674
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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