Water → 2-(3,5-Dichloro-pyridin-4-yl)-1-(2,3-diethoxy-4-methoxy-phenyl)-ethanone

HRID 456033Notes

Reaction equation

HRID 456033 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([OH:19])[C:12]=1O)=[O:10].[C:22]([O-:25])([O-])=O.[K+].[K+].[CH2:28](I)[CH3:29].O.[CH3:32]N(C=O)C>>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH2:28][CH3:29])[C:12]=1[O:25][CH2:22][CH3:32])=[O:10]

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 227343312-(3,5-Dichloro-pyridin-4-yl)-1-(2,3-dihydroxy-4-methoxy-phenyl)-ethanone

Product 1

HCID 249588592-(3,5-Dichloro-pyridin-4-yl)-1-(2,3-diethoxy-4-methoxy-phenyl)-ethanone

Procedure

2-(3,5-Dichloro-pyridin-4-yl)-1-(2,3-dihydroxy-4-methoxy-phenyl)-ethanone (450 mg, 1.4 mmol) from preparation 3 was dissolved in dry DMF (10 mL). K2CO3 (566 mg, 4.1 mmol) was added followed by Ethyl Iodide (442 μL, 5.5 mmol). The reaction mixture was stirred at rt overnight. Water (10 mL) was added and the organic products were extracted with EtOAc (2×25 mL). The combined organic phases were washed with water (10 mL) and brine (10 mL) and then dried over MgSO4. The solvent was removed in vacuo and the pure product obtained be standard silica gel chromatography to provide 2-(3,5-Dichloro-pyridin-4-yl)-1-(2,3-diethoxy-4-methoxy-phenyl)-ethanone as a white solid. Yield 220 mg (42%). The compound was redissolved in DCM (1 mL) under argon. BCl3 (0.97 mL of a 1M solution in DCM) was added slowly at room temperature. EtOH (2 mL) was added slowly after 2 hours. The solvent were removed in vacuo and the pure product obtained be standard silica gel chromatography to provide 2-(3,5-Dichloro-pyridin-4-yl)-1-(3-ethoxy-2-hydroxy-4-methoxyphenyl)-ethanone was obtained as a white solid. 1H NMR (DMSO-d6) δ=11.36 (1H, s), 8.67 (2H, s), 7.88 (1H, d), 6.77 (1H, d), 4.80 (2H, s), 3.96 (2H, q), 3.91 (3H, s), 1.26 (3H, t). Yield 100 mg (49%)

Workup

  1. extractionthe organic products were extracted with EtOAc (2×25 mL)
  2. washThe combined organic phases were washed with water (10 mL) and brine (10 mL)
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed in vacuo
  5. customthe pure product obtained

Sources & evidence

ORD record
ord-dd2752e1a1ca45759bf3529455b043b9
Source dataset
uspto-grants-2013_07
Patent number
US08497380B2

Reaction notes

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