Acetic Acid → HCID 86588462, compound

HRID 896053Notes

Reaction equation

HRID 896053 reaction equation
[CH3:1][O:2][C:3](=[O:21])[CH2:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]#[C:16][Si](C)(C)C)[CH:13]=2)[CH:8]=[N:7][CH:6]=1.C([O-])([O-])=O.[K+].[K+].C(O)(=O)C>CO>[CH3:1][O:2][C:3](=[O:21])[CH2:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]#[CH:16])[CH:13]=2)[CH:8]=[N:7][CH:6]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 11430Potassium Carbonate2×HCID 69201512HCID 69201512, compound

Product 1

HCID 86588462HCID 86588462, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (6-trimethylsilanylethynyl-isoquinolin-4-yl)-acetic acid methyl ester, as prepared for Intermediate 32 (0.19 g, 0.64 mmol), in anhydrous methanol (7 ml) is added K2CO3 (72 mg) and the resulting mixture stirred for 1 h. Additional K2CO3 (11 mg) is then added and stirring continued for 30 min. The mixture is then neutralized with glacial acetic acid and concentrated. Purification by flash silica column chromatography (ethylacetate/hexane 1:1) gives (6-ethynyl-isoquinolin4-yl)-acetic acid methyl ester M+ 225. This intermediate (79 mg, 0.35 mmol) is dissolved in methanol under an inert atmosphere and 10% Pd on carbon (79 mg) added. The resulting suspension is stirred vigorously under an atmosphere of gaseous hydrogen. After 90 mins, filtration, washing with methanol and concentration give (6-ethyl-isoquinolin-4-yl)-acetic acid methyl ester MW 229. To a solution of this intermediate (68 mg, 0.30 mmol) in THF/methanol/water (3:1:1, 3.5 ml) is added LiOH (12.5 mg) and the mixture stirred for 20 h at room temperature. Concentration under reduced pressure gives lithium (6-ethyl-isoquinolin4-yl)-acetate M+ 221.

Workup

  1. stirringstirring
  2. waitcontinued for 30 min
  3. concentrationconcentrated
  4. customPurification by flash silica column chromatography (ethylacetate/hexane 1:1)

Sources & evidence

ORD record
ord-26d4c16c23dc4a4d98c09fa703041aa3
Source dataset
uspto-grants-2005_07
Patent number
US06919337B2

Reaction notes

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