Hydrochloric Acid → 5-Hydroxy-2-(3-methyl-butyl)-3-oxo-6-thiophen-2-yl-2,3-dihydro-pyridazine-4-carboxylic acid ethyl ester

HRID 30978노트

반응식

HRID 30978 반응식
C(O[C:4](=[O:26])[C:5](=[N:11][N:12]([C:18](=[O:25])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:6]1[S:7][CH:8]=[CH:9][CH:10]=1)C.[O-]CC.[Na+].Cl>CCO>[CH2:23]([O:22][C:20]([C:19]1[C:18](=[O:25])[N:12]([CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[N:11]=[C:5]([C:6]2[S:7][CH:8]=[CH:9][CH:10]=2)[C:4]=1[OH:26])=[O:21])[CH3:24]

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 72394125[(2-Ethoxycarbonyl-acetyl)-(3-methyl-butyl)-hydrazono]-thiophen-2-yl-acetic acid ethyl ester

생성물 1

HCID 597914415-Hydroxy-2-(3-methyl-butyl)-3-oxo-6-thiophen-2-yl-2,3-dihydro-pyridazine-4-carboxylic acid ethyl ester수율 83.2%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

To a solution of [(2-Ethoxycarbonyl-acetyl)-(3-methyl-butyl)-hydrazono]-thiophen-2-yl-acetic acid ethyl ester (12a) (380 mg, 1.0 mmol) in EtOH (6 mL) at room temperature, sodium ethoxide (Aldrich) (21 wt % in ethanol, 0.4 mL, 1.1 mmol) was added, and the resulting mixture was stirred for 30 min. Aqueous HCl (5%, 0.75 mL) was added slowly, and then followed by liquid-liquid extraction with H2O/EtOAc. The combined organic layer was washed with brine, dried over MgSO4, concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel to give the desired product (13a) (280 mg, 83%) as yellow solid. LC-MS (ESI+): m/e=337.30 [M+1]+(exact ms: 336.11); 1H NMR (400 MHz, CDCl3): δ 7.89 (dd, 1H, J=3.6, 1.2 Hz), 7.39 (dd, 1H, J=5.2, 1.2 Hz), 7.10 (dd, 1H, J=5.2, 3.6 Hz), 4.53 (q, 2H, J=7.2 Hz), 4.22 (m, 2H), 1.73 (m, 2H), 1.68 (m, 1H), 1.50 (t, 3H, J=7.2 Hz), 0.99 (d, 6H, J=6.4 Hz).

후처리

  1. extractionfollowed by liquid-liquid extraction with H2O/EtOAc
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customthe residue was purified by flash chromatography on silica gel

출처 및 근거

ORD 기록
ord-a4c0df31ae8940cabdc18cf7376b4cc7
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425552B2

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