Sodium hydride → HCID 18366002, compound

HRID 380733Notes

Reaction equation

HRID 380733 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][CH3:19])[CH2:16][O:15][CH2:14]1.[NH2:20][C:21]1[C:26]([Cl:27])=[CH:25][N:24]=[CH:23][C:22]=1[Cl:28].[H-].[Na+]>C(Cl)(=O)C(Cl)=O.O1CCCC1>[Cl:28][C:22]1[CH:23]=[N:24][CH:25]=[C:26]([Cl:27])[C:21]=1[NH:20][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][CH3:19])[CH2:16][O:15][CH2:14]2)[CH:5]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 898884-Amino-3,5-dichloropyridineHCID 18366001HCID 18366001, compound2×

Product 1

HCID 18366002HCID 18366002, compoundYield 78.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 65578Oxalyl chlorideSolvent

Procedure

1.0 g (3.7 mmol) of 4-methoxy-3-(4-methoxytetrahydrofuran-3-yloxy)benzoic acid (starting compound A1) is heated to reflux for 2 h in 4 ml of oxalyl chloride. Excess oxalyl chloride is removed in vacuo and coevaporated using 2×20 ml of toluene. A solution of 600 mg (3.7 mmol) of 4-amino-3,5-dichloropyridine in 10 ml of tetrahydrofuran is added dropwise to a suspension of 220 mg (7.4 mmol) of 80% strength sodium hydride in 10 ml of tetrahydrofuran. The mixture is stirred for 1 h at RT, the acid chloride is then added dropwise in a further 10 ml of tetrahydrofuran and the reaction mixture is stirred at RT overnight. It is concentrated, the residue is treated with 50 ml of water and the mixture is extracted with 3×50 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, concentrated and the residue is crystallized from 50 ml of isopropanol. 1.2 g of the title compound of m.p. 175-177° C. are obtained.

Workup

  1. customExcess oxalyl chloride is removed in vacuo
  2. stirringthe reaction mixture is stirred at RT overnight
  3. concentrationIt is concentrated
  4. additionthe residue is treated with 50 ml of water
  5. extractionthe mixture is extracted with 3×50 ml of dichloromethane
  6. dry with materialThe combined organic phases are dried over magnesium sulfate
  7. concentrationconcentrated
  8. customthe residue is crystallized from 50 ml of isopropanol

Sources & evidence

ORD record
ord-25815656485c42d5aeb2a1c354a6541c
Source dataset
uspto-grants-2001_10
Patent number
US06303789B1

Reaction notes

Loading…