Thionyl Chloride → HCID 57707796, compound

HRID 1397684Notes

Reaction equation

HRID 1397684 reaction equation
[Cl:1][C:2]1[C:11]([CH2:12]O)=[CH:10][C:9]2[C:4](=[C:5]([Cl:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.O=S(Cl)Cl.[N-:19]=[N+:20]=[N-:21].[Na+]>C(Cl)(Cl)Cl>[N:19]([CH2:12][C:11]1[C:2]([Cl:1])=[N:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[Cl:14])=[N+:20]=[N-:21]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 33557Sodium AzideHCID 57707778HCID 57707778, compound

Product 1

HCID 57707796HCID 57707796, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A solution of (2,8-dichloroquinolin-3-yl)methanol (228 mg, 1 mmol) in CHCl3 (4 mL) was treated with SOCl2 (0.36 mL, 5 eq) dropwise, and the reaction was stirred at rt for 2 h before removal of solvents and the residue was partitioned between EtOAc and NaHCO3. The organic was separated and dried over Na2SO4. Solvents were removed under reduced pressure and the residue was dried under vacuum. The residue was dissolved in DMSO (2 mL) and treated with NaN3 (72 mg, 1.1 eq) at rt. LCMS showed completion after 4 h. The reaction mixture was partitioned between EtOAc (2 mL) and water (1 mL), and the water layer was extracted with EtOAc (5 mL) once and combined organics were washed with water, brine, dried over Na2SO4 and concentrated to give a pale yellow solid as 3-(azidomethyl)-2,8-dichloroquinoline (215 mg, 85%, 2 steps). This solid (50 mg, 0.2 mmol) in DCM (2 mL) was treated with piperidine (143 μL, 7.3 eq) in EtOH (2 mL) at reflux over night. The reaction was worked up and the residue was purified by column chromatography on silica gel (eluent: EtOAc/hexane, 1/5) to give a yellow solid (30 mg, 50%). 1H NMR (400 MHz, CDCl3) δ ppm 8.01 (1 H, s), 7.62 (1 H, t, J=8.0 Hz), 7.53 (1 H, d, J=8.0 Hz), 7.49 (1H, d, J=8.0 Hz), 4.02 (2H, s), 3.26-3.23 (m, 4H), 1.74-1.58 (m, 6H). Mass Spectrum (ESI) m/e=302 (M+1).

Workup

  1. customthe residue was partitioned between EtOAc and NaHCO3
  2. customThe organic was separated
  3. dry with materialdried over Na2SO4
  4. customSolvents were removed under reduced pressure
  5. customthe residue was dried under vacuum
  6. dissolutionThe residue was dissolved in DMSO (2 mL)
  7. customafter 4 h
  8. customThe reaction mixture was partitioned between EtOAc (2 mL) and water (1 mL)
  9. extractionthe water layer was extracted with EtOAc (5 mL) once
  10. washcombined organics were washed with water, brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-c0e4a22b6b7040e59c9168271142ff9f
Source dataset
uspto-grants-2014_12
Patent number
US08901135B2

Reaction notes

Loading…