Phosphorus oxychloride → HCID 86683175, compound

HRID 1852066Notes

Reaction equation

HRID 1852066 reaction equation
[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C:11]3[N:12]=[C:13](O)[C:14]4[C:19]([CH:20]=3)=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=4)[CH:9]=[CH:10][C:2]1=2.O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:13]1[C:14]2[C:19](=[CH:18][C:17]([O:21][CH3:22])=[CH:16][CH:15]=2)[CH:20]=[C:11]([C:8]2[CH:9]=[CH:10][C:2]3[O:1][CH2:6][CH2:5][O:4][C:3]=3[CH:7]=2)[N:12]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487726HCID 178487726, compound

Product 1

HCID 86683175HCID 86683175, compoundYield 75.5%

Procedure

A solution of 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-methoxyisoquinolin-1-ol (250 mg, 0.808 mmol) in POCl3 (5 mL, 53.6 mmol) was refluxed for 14 h. Concentrated the solvent. The residue was taken into a mixture of DCM and 4N NaOH solution. Adjust pH to 7. The organic phase was collected and dried over sodium sulfate, filtered, then concentrated under vacuum. The crude material was purified by silica gel chromatography using 10% EtOAc/Hexanes as eluent to give 200 mg of the desired product 1-chloro-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-methoxyisoquinoline as a solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.18 (d, J=9.3 Hz, 1H), 7.77 (s, 1H), 7.65-7.55 (m, 2H), 7.21 (dd, J=9.2, 2.4 Hz, 1H), 7.08 (d, J=2.3 Hz, 1H), 6.95 (d, J=8.3 Hz, 1H), 4.30 (s, 4H), 3.95 (s, 3H).

Workup

  1. concentrationConcentrated the solvent
  2. additionThe residue was taken into a mixture of DCM and 4N NaOH solution
  3. customThe organic phase was collected
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-780a704d4626442086e6bce755f36a89
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

Loading…