Water → Methyl 3-[(3-Cyanopyrazin-2-yl)thio]propanoate

HRID 502569Notes

Reaction equation

HRID 502569 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[N:6][CH:5]=[CH:4][N:3]=1.[SH:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14].C[O-].[Na+].O>CN(C)C=O>[C:8]([C:7]1[C:2]([S:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[N:3][CH:4]=[CH:5][N:6]=1)#[N:9]

Participants

6

Reactant 4

HCID 962WaterHCID 18050Methyl 3-mercaptopropionateHCID 2924653-Chloropyrazine-2-carbonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 57436555Methyl 3-[(3-Cyanopyrazin-2-yl)thio]propanoateYield 43.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-chloro-3-cyanopyrazine (9.9 g, 73.8 mmol) and methyl 3-mercaptopropionate (9.36 mL, 84.5 mmol) in anhydrous dimethylformamide (40 mL) cooled to 4° C. was added solid sodium methoxide (4.7 g, 87.0 mmol). The reaction mixture was allowed to warm to room temperature overnight. The mixture was poured into water and extracted twice with ethyl acetate. The combined organic layers were washed once saturated aqueous sodium bicarbonate solution, five times with brine, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography, on silica gel, eluting with a mixture of 7:3 hexanes:ethyl acetate gave methyl 3-(3-cyanopyrazin-2-ylthio)propanoate (7.2 g) as a pale yellow liquid. 1H NMR (300 MHz, CDCl3): 8.51 (d, 1H), 8.32 (d, 1H), 3.72 (s, 3H), 3.50 (t, 2H), 2.79 ppm (t, 2H). MW=223 confirmed by LC-MS, tr=11.11 min (Method Y) MH+=221-225.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic layers were washed once saturated aqueous sodium bicarbonate solution, five times with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography
  7. washon silica gel, eluting with a mixture of 7:3 hexanes

Sources & evidence

ORD record
ord-e68e905cea3c49d583f996052bd188a8
Source dataset
uspto-grants-2010_08
Patent number
US07776847B2

Reaction notes

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