Sodium hydride → (S)-2-(1-methyl-2-pyrrolidinylmethoxy)pyrazine

HRID 617285

Reaction equation

HRID 617285 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][OH:8].[H-].[Na+].Cl[C:12]1[CH:17]=[N:16][CH:15]=[CH:14][N:13]=1>C1COCC1>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][O:8][C:12]1[CH:17]=[N:16][CH:15]=[CH:14][N:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 73277ChloropyrazineHCID 643492(2S)-1-Methyl-2-pyrrolidinemethanol

Product 1

HCID 44325872(S)-2-(1-methyl-2-pyrrolidinylmethoxy)pyrazineYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(S)-(-)-1-Methyl-2-pyrrolidinemethanol (Aldrich Chemical Co., 0.5 g, 4.34 mmol) was dissolved in anhydrous THF and brought to 0° C. NaH ((80% dispersion in mineral oil), 131 g, 4.56 mmol) was added and the reaction mixture was allowed to warm to room temperature with stirring. After 30 minutes 2-chloropyrazine (0.497 g, 4.34 mmol) was added via syringe. The mixture was stirred for 48 hours. The solvent was then evaporated in vacuo and the mixture diluted with chloroform, washed with saturated NaHCO3 and a brine solution. The organic layer was then dried over MgSO4. The resulting crude material was purified by flash chromatography (10% MeOH/CHCl3) to give 0.81 g (97% yield) of the title compound as an oil. TLC Rf =0.3 (10% MeOH/CHCl3). MS (DCI/NH3) m/e 194 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.24 (d, J=1.5 Hz, 1H, 8.11 (d, J=3 Hz, 1H), 8.07 (dd, J=3, 1.5 Hz, 1H), 4.36 (dd, J=9, 6 Hz, 1H), 4.28 (dd, J=9, 6 Hz, 1H), 3.16-3.08 (m, 1H, 2.7-2.58 (m, 1H, 2.47 (s, 3H), 2.34-2.24 (m, 1H, 2.08-1.93 (m, 1H, 1.91-1.67 (m, 3H).

Workup

  1. custombrought to 0° C
  2. stirringThe mixture was stirred for 48 hours
  3. customThe solvent was then evaporated in vacuo
  4. additionthe mixture diluted with chloroform
  5. washwashed with saturated NaHCO3
  6. dry with materialThe organic layer was then dried over MgSO4
  7. customThe resulting crude material was purified by flash chromatography (10% MeOH/CHCl3)

Sources & evidence

ORD record
ord-bce61a14f88c4b30ac79a275727ce2e8
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Linked notes

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