Hydrochloric Acid → 6-(4-Chloro-phenyl)-5-cyclopropylmethoxy-pyrazine-2-carboxylic acid

HRID 1958158Notes

Reaction equation

HRID 1958158 reaction equation
[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].Br[C:9]1[N:10]=[CH:11][C:12]([C:22]([OH:24])=[O:23])=[N:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1.Cl>CN(C=O)C.O>[Cl:21][C:18]1[CH:17]=[CH:16][C:15]([C:14]2[N:13]=[C:12]([C:22]([OH:24])=[O:23])[CH:11]=[N:10][C:9]=2[O:5][CH2:4][CH:1]2[CH2:3][CH2:2]2)=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 24758Sodium hydride2×HCID 75644Cyclopropanemethanol2×HCID 866169645-Bromo-6-(4-chloro-phenyl)-pyrazine-2-carboxylic acid

Product 1

HCID 672821826-(4-Chloro-phenyl)-5-cyclopropylmethoxy-pyrazine-2-carboxylic acidYield 86.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent3×

Procedure

Cyclopropylmethanol (1.54 g, 1.73 ml, 21.3 mmol) was diluted in dried DMF (15 mL); sodium hydride (512 mg, 21.3 mmol) was added in portions and the reaction mixture was stirred at room temperature for 15 minutes. The resulting solution was added slowly at <5° C. to a solution of 5-bromo-6-(4-chlorophenyl)pyrazine-2-carboxylic acid (CAN 960247-80-7; 3.040 g, 9.7 mmol) in dried DMF (15 mL). The reaction mixture was stirred at room temperature for 30 minutes; water was added and the mixture was acidified with 1M HCl solution to pH=2. The mixture was extracted with ethyl acetate; organic phases were combined, dried with MgSO4 and concentrated in vacuo. The crude did still contain starting material and was dissolved again in 15 mL DMF; a solution of cyclopropylmethanol (1.05 g, 1.18 ml, 14.5 mmol) and sodium hydride (582 mg, 14.5 mmol) in 15 mL DMF was added and the mixture was stirred at room temperature for 3 hours. Water was added and the reaction mixture was acidified with 1M HCl solution to pH 2; the product precipitated to give 2.55 g (86%) of the title compound as light yellow solid; MS (ESI) 303.2 (M−H)−.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated in vacuo
  5. dissolutionwas dissolved again in 15 mL DMF
  6. stirringthe mixture was stirred at room temperature for 3 hours
  7. customthe product precipitated

Sources & evidence

ORD record
ord-d545eacf015549e695980b1b1d7af3d5
Source dataset
uspto-grants-2013_04
Patent number
US08410107B2

Reaction notes

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