Ethyl bromoacetate → Ethyl 2-((1-chloroisoquinolin-6-yl)oxy)acetate

HRID 1852157Notes

Reaction equation

HRID 1852157 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:19]([O:22][CH2:23][CH3:24])(=[O:21])[CH3:20].BrCC(OCC)=O>CC(C)=O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH2:20][C:19]([O:22][CH2:23][CH3:24])=[O:21])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 1357421771-chloro-2H-isoquinolin-6-one

Product 1

HCID 86683225Ethyl 2-((1-chloroisoquinolin-6-yl)oxy)acetate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

To a dry 40 mL vial equipped with a stir bar was added 1-chloroisoquinolin-6-ol (200 mg, 1.11 mmol) and potassium carbonate (231 mg, 1.67 mmol). To the vial was added dry ethyl acetate (6 mL) followed by ethyl 2-bromoacetate (0.148 mL, 1.34 mmol). The vial was sealed and then heated at 60° C. for 2 h. The mixture was cooled to room temperature, diluted with acetone, and then filtered. The filtrated was concentrated and the resulting solid residue was subjected to SiO2 chromatography (hexanes:EtOAc 85:15 to 70:30) to afford ethyl 2-((1-chloroisoquinolin-6-yl)oxy)acetate as a colorless, crystalline solid (296 mg, 66%). 1H NMR (400 MHz, CHLOROFORM-d) δ 8.29 (d, J=9.3 Hz, 1H), 8.22 (d, J=5.8 Hz, 1H), 7.49 (d, J=5.8 Hz, 1H), 7.40 (dd, J=9.3, 2.8 Hz, 1H), 7.04 (d, J=2.5 Hz, 1H), 4.79 (s, 2H), 4.32 (q, J=7.3 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H); MS: MS m/z 266.15 (M++1).

Workup

  1. customTo a dry 40 mL vial equipped with a stir bar
  2. customThe vial was sealed
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrated was concentrated

Sources & evidence

ORD record
ord-a6704c90b51d45228ca046f798a6e897
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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