Acetic Acid → N-hydroxy-1-oxo-1,2-dihydroisoquinoline-7-carboxamide

HRID 1616105ノート

反応式

HRID 1616105 の反応式
Cl.[NH2:2][OH:3].[OH-].[K+].NO.[O:8]=[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]([O:21]C)=O)[CH:17]=2)[CH:12]=[CH:11][NH:10]1.C(O)(=O)C>CO>[OH:3][NH:2][C:19]([C:16]1[CH:17]=[C:18]2[C:13]([CH:12]=[CH:11][NH:10][C:9]2=[O:8])=[CH:14][CH:15]=1)=[O:21]

参加物

7

反応物 5

HCID 176Acetic AcidHCID 787HydroxylamineHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 60075037Methyl 1-oxo-1,2-dihydroisoquinoline-7-carboxylate

生成物 1

HCID 56961768N-hydroxy-1-oxo-1,2-dihydroisoquinoline-7-carboxamide収率 37%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒3 回

反応条件

温度
90 °C

実験手順

A mixture of hydroxylamine hydrochloride (2.0 g, 29 mmol) in methanol (10 mL) was heated at 90° C. under a dry nitrogen atmosphere until homogeneous. To this heated solution was added a solution of potassium hydroxide (2.85 g, 50.8 mmol) in methanol (6 mL). A precipitate formed on mixing. After heating at 90° C. for 30 minutes, the mixture was cooled to rt and the solids were allowed to settle. The resulting solution was assumed to contain 1.7 M hydroxylamine.potassium salt and was carefully removed by syringe to exclude solids. An aliquot of the above solution (1.0 mL, 1.7 mmol) was added to a solution of methyl 1-oxo-1,2-dihydroisoquinoline-7-carboxylate (32.5 mg, 0.16 mmol) in methanol (1 mL). After stirring for 1 h at rt, excess reagent was quenched by the addition of acetic acid (0.20 mL, 3.52 mmol). The mixture was concentrated to dryness and the residue was twice co-evaporated with toluene. The crude product was purified by preparative HPLC to afford N-hydroxy-1-oxo-1,2-dihydroisoquinoline-7-carboxamide (12 mg, 37%). LC-MS: (FA) ES+ 205; 1H NMR (300 MHz, MeOD) δ 8.67 (d, J=1.5 Hz, 1H), 8.06 (dd, J=8.3, 1.9 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.26 (d, J=7.1 Hz, 1H), 6.70 (d, J=7.3 Hz, 1H).

後処理

  1. customA precipitate formed
  2. additionon mixing
  3. temperatureAfter heating at 90° C. for 30 minutes
  4. temperaturethe mixture was cooled to rt
  5. custompotassium salt and was carefully removed by syringe
  6. concentrationThe mixture was concentrated to dryness
  7. customThe crude product was purified by preparative HPLC

出典と根拠

ORDレコード
ord-7cb510f831ea44609ed8cdd127609546
出典データセット
uspto-grants-2014_07
特許番号
US08765773B2

反応ノート

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