Water → HCID 135907980, compound

HRID 1522839Notes

Reaction equation

HRID 1522839 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)=[N:8][CH:7]=[CH:6]2.B(Br)(Br)Br.O.CCOC(C)=O>C(Cl)Cl>[N:16]1([CH2:15][CH2:14][O:13][C:9]2[C:10]3[C:5](=[CH:4][C:3]([OH:2])=[CH:12][CH:11]=3)[CH:6]=[CH:7][N:8]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 25134Boron tribromideHCID 67465008HCID 67465008, compound

Product 1

HCID 135907980HCID 135907980, compoundYield 70.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-Methoxy-1-(2-(piperidin-1-yl)ethoxy)isoquinoline (0.60 g, 2.10 mmol) was dissolved in 30 mL of dry CH2Cl2 at room temperature. BBr3 (10.50 mmol, 10.50 mL of 1.0 M CH2Cl2 solution) was added dropwise with stirring via a syringe at room temperature. The reaction solution was allowed to stir overnight at room temperature. The mixture was cooled to 0° C. in an ice bath and hydrolyzed by adding water. EtOAc was added to partition the solution. The organic layer was separated; the aqueous layer was extracted with EtOAc twice. The organic layers were combined, washed with brine and dried over anhydrous MgSO4. The solvent was removed under vacuum. The residue was purified by flash column chromatography using silica-gel with CH3OH/CH2Cl2 (1/9 v/v) to give a white solid product, 40 g, 70.2% yield. MS: 273.2 [M+H]+. 1H NMR (DMSO-d6, 300 MHz) δ 10.29 (s, 1H), 8.05 (d, 1H, J=8.7 Hz), 7.32 (d, 1H, J=7.2 Hz), 6.93 (d, 1H, J=8.4 Hz), 6.87 (s, 1H), 6.43 (d, 1H, J=7.2 Hz), 4.03 (s, br, 2H), 2.62 (s, br, 2H), 2.50 (s, br, 2H), 1.49-1.39 (m, 6H).

Workup

  1. stirringto stir overnight at room temperature
  2. temperatureThe mixture was cooled to 0° C. in an ice bath
  3. customto partition the solution
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc twice
  6. washwashed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. customThe solvent was removed under vacuum
  9. customThe residue was purified by flash column chromatography
  10. customto give a white solid product, 40 g, 70.2% yield

Sources & evidence

ORD record
ord-82f5202037c640ad973f3287cb57b553
Source dataset
uspto-grants-2015_07
Patent number
US09078888B2

Reaction notes

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