Sodium hydride → HCID 9825424, compound

HRID 380735Notes

Reaction equation

HRID 380735 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[O:12][CH:13]1[CH:17]([O:18][CH2:19][S:20][CH3:21])[CH2:16][O:15][CH2:14]1.[NH2:22][C:23]1[C:28]([Cl:29])=[CH:27][N:26]=[CH:25][C:24]=1[Cl:30].[H-].[Na+]>C(Cl)(=O)C(Cl)=O.O1CCCC1>[Cl:30][C:24]1[CH:25]=[N:26][CH:27]=[C:28]([Cl:29])[C:23]=1[NH:22][C:7](=[O:9])[C:6]1[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[C:4]([O:12][CH:13]2[CH:17]([O:18][CH2:19][S:20][CH3:21])[CH2:16][O:15][CH2:14]2)[CH:5]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 898884-Amino-3,5-dichloropyridineHCID 18365998HCID 18365998, compound

Product 1

HCID 9825424HCID 9825424, compoundYield 20.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 65578Oxalyl chlorideSolvent

Procedure

1.0 g (3.2 mmol) of 4-methoxy-3-(4-methylthiomethyloxytetrahydrofuran-3-yloxy)benzoic acid (starting compound A19) are heated to reflux for 90 min in 4 ml of oxalyl chloride. Excess oxalyl chloride is removed in vacuo and coevaporated using 2×20 ml of toluene. A solution of 520 mg (3.2 mmol) of 4-amino-3,5-dichloropyridine in 10 ml of tetrahydrofuran is added dropwise to a suspension of 200 mg (6.9 mmol) of 80% strength sodium hydride in 10 ml of tetrahydrofuran. The mixture is stirred at RT for 90 min, then the acid chloride is added dropwise in a further 10 ml of tetrahydrofuran and the reaction mixture is stirred at RT for 2 h. It is concentrated, the residue is treated with 25 ml of water and the mixture is extracted with 3×25 ml of ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over magnesium sulfate, concentrated and the residue is chromatographed on silica gel. The product-containing fractions are concentrated and the residue is crystallized from acetonitrile. 300 mg of the title compound of m.p. 195-198° C. are obtained.

Workup

  1. customExcess oxalyl chloride is removed in vacuo
  2. stirringthe reaction mixture is stirred at RT for 2 h
  3. concentrationIt is concentrated
  4. additionthe residue is treated with 25 ml of water
  5. extractionthe mixture is extracted with 3×25 ml of ethyl acetate
  6. washThe combined organic phases are washed with saturated sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customthe residue is chromatographed on silica gel
  10. concentrationThe product-containing fractions are concentrated
  11. customthe residue is crystallized from acetonitrile

Sources & evidence

ORD record
ord-64e354c2a17b48229f3734c3d41fe917
Source dataset
uspto-grants-2001_10
Patent number
US06303789B1

Reaction notes

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