Acetic Acid → HCID 86588462, compound

HRID 1745814Notes

Reaction equation

HRID 1745814 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 neutralised with glacial acetic acid and concentrated. Purification by flash silica column chromatography (ethylacetate/hexane 1:1) gives (6-ethynyl-isoquinolin-4-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 M+ 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-isoquinolin-4-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-67f305a0be4e47359685e31dacc2748f
Source dataset
uspto-grants-2006_03
Patent number
US07019136B2

Reaction notes

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