Hydrochloric Acid → 5-Hydroxy-2-(2-methoxyethoxy)isonicotinaldehyde

HRID 1484775ノート

反応式

HRID 1484775 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:8]([O:11]COC)=[CH:9][N:10]=1)[CH:6]=[O:7].Cl.[C:16]([O-])([O-])=[O:17].[K+].[K+].C1[CH2:26][O:25][CH2:24]C1>O>[OH:11][C:8]1[C:5]([CH:6]=[O:7])=[CH:4][C:3]([O:2][CH2:1][CH2:24][O:25][CH3:26])=[N:10][CH:9]=1.[OH:11][C:8]1[CH:9]=[N:10][C:3]([O:2][CH2:1][CH2:24][O:25][CH3:26])=[C:4]([CH:5]=1)[CH:16]=[O:17]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 121807202-Methoxy-5-(methoxymethoxy)-4-pyridinecarboxaldehyde

生成物 2

HCID 866907685-Hydroxy-2-(2-methoxyethoxy)isonicotinaldehyde収率 60%HCID 866907695-Hydroxy-2-(2-methoxyethoxy)nicotinaldehyde収率 11%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
50 °C

実験手順

To a solution of 2-methoxy-5-(methoxymethoxy)isonicotinaldehyde (1.27 g, 5.29 mol) in THF (5 mL) was added HCl (3 N, 4 mL). The reaction was stirred at 50° C. for 1 h, cooled to RT, and diluted with water (5 mL). The mixture was neutralized to pH 7-8 with solid K2CO3 and the aqueous layer was extracted with EtOAc (100 mL) twice. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes to give 5-hydroxy-2-(2-methoxyethoxy)isonicotinaldehyde (630 mg, 60%) and 5-hydroxy-2-(2-methoxyethoxy)nicotinaldehyde (120 mg, 11%). Data for 5-hydroxy-2-(2-methoxyethoxy)isonicotinaldehyde: 1H NMR (400 MHz, CDCl3) δ 9.98 (s, 1H), 9.50 (s, 1H), 8.07 (s, 1H), 7.02 (s, 1H), 4.51-4.39 (m, 2H), 3.81-3.72 (m, 2H), 3.47 (s, 3H). LRMS (M+H+) m/z 198.1. Data for and 5-hydroxy-2-(2-methoxyethoxy)nicotinaldehyde: NMR (400 MHz, CDCl3) δ 10.3 (s, 1H), 7.99 (d, J=3.2 Hz, 1H), 7.58 (d, J=3.2 Hz, 1H), 7.18-7.07 (br, 1H), 4.54 (dd, J=5.4, 3.7 Hz, 2H), 3.84 (dd, J=5.4, 3.7 Hz, 2H), 3.49 (s, 3H); MS (ESI) m/z 198.1 [M+H]+.

後処理

  1. temperaturecooled to RT
  2. extractionthe aqueous layer was extracted with EtOAc (100 mL) twice
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified on silica gel using
  6. additiona mixture of EtOAc and hexanes

出典と根拠

ORDレコード
ord-450f55298953409caf5bc6746f8dbbf2
出典データセット
uspto-grants-2016_08
特許番号
US09422279B2

反応ノート

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