Potassium Carbonate → HCID 68874974, compound

HRID 1435994Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH:6]=[CH:5]2.C(=O)([O-])[O-].[K+].[K+].[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH2:29][C@@H:28](OS(C)(=O)=O)[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>CN(C)C=O>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][CH2:29][C@H:28]([O:1][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[C:8](=[O:12])[NH:7][CH:6]=[CH:5]3)[CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

Conditions

Temperature: 100 °C

Procedure

6-Hydroxy-2H-isoquinolin-1-one (2 g, 12.41 mmol) and potassium carbonate (3.43 g, 2 mol) were mixed with N, N-dimethylformamide (40 ml) at 100° C. A solution of (R)-3- methanesulphonyloxypiperidine-1-carboxylic acid tert-butyl ester (5.2 g, 1.5 mol) in dimethylformamide (50 ml) was added dropwise over 15 minutes. The mixture was stirred at 100° C. for 3.5 hours and allowed to cool. The crude material was partitioned between ethyl acetate and water. The ethyl acetate layer was separated and washed with sodium hydroxide (2M) then brine and dried over magnesium sulphate. The residue was purified by flash chromatography on silica (eluent: 0-100% Heptane/Ethyl acetate followed by 5% 2M ammonia in methanol/ethyl acetate) to give (S)-3-(Oxo-1,2-dihydroisoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (1.25g, 29%), El-MS: m/z=345.3 [M+H]+.

Workup

temperatureto cool
customThe crude material was partitioned between ethyl acetate and water
customThe ethyl acetate layer was separated
washwashed with sodium hydroxide (2M)
dry with materialbrine and dried over magnesium sulphate
customThe residue was purified by flash chromatography on silica (eluent: 0-100% Heptane/Ethyl acetate followed by 5% 2M ammonia in methanol/ethyl acetate)

Sources & evidence

ORD record: ord-a21657856a784a97af3338f21f8d1a45
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618985B2

Reaction notes

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