Phenol → 4-Hydroxy-1-phenoxy-isoquinoline-3-carboxylic acid butyl ester
Reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](Cl)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].[C:20]1([OH:26])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[OH-].[Na+]>>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([O:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]Participants
Procedure
A mixture of 1.399 g of 1-Chloro-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (5 mmol) and 2.86 g of phenol was heated at 145° C. to 150° C. for 24 h. After cooling to ambient temperature the mixture was suspended in 50 ml of aqueous 2N NaOH and the mixture was extracted with 4×25 ml of ethyl acetate. The combined organic phases were washed with 3×25 ml of aqueous 2N NaOH, 50 ml of brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with hexanes:ethyl acetate (9:1) and (95:5). 0.650 g of the title compound were obtained; 1H NMR (CDCl3): δ=11.52 (s, 1H), 8.32 to 8.39 (m, 2H), 7.72 to 7.86 (m, 2H), 7.13 to 7.42 (m, 5H), 4.31 (t, 2H), 1.69 (m, 2H), 1.37 (m, 2H), 0.93 (t, 3H).
Workup
- temperaturewas heated at 145° C. to 150° C. for 24 h
- extractionthe mixture was extracted with 4×25 ml of ethyl acetate
- washThe combined organic phases were washed with 3×25 ml of aqueous 2N NaOH, 50 ml of brine
- dry with materialdried over MgSO4
- customevaporated in vacuo
- customThe residue was purified by flash column chromatography on silica gel eluting with hexanes:ethyl acetate (9:1) and (95:5)
Sources & evidence
- ORD record
- ord-4eef133f5e3a4e06aa5bd3c134b24680
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08278325B2
Reaction notes
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