Sodium hydride → 3-Ethynyl-5-[[(2S)-1-methyl-2-pyrrolidinyl]methoxy]pyridine

HRID 1660724Notes

Reaction equation

HRID 1660724 reaction equation
OC(C)(C)[C:3]#[C:4][C:5]1[CH:6]=[C:7]([O:11][CH2:12][C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[CH3:18])[CH:8]=[N:9][CH:10]=1.[H-].[Na+]>C1(C)C=CC=CC=1>[C:4]([C:5]1[CH:6]=[C:7]([O:11][CH2:12][C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[CH3:18])[CH:8]=[N:9][CH:10]=1)#[CH:3]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 11471333HCID 11471333, compound

Product 1

HCID 114132863-Ethynyl-5-[[(2S)-1-methyl-2-pyrrolidinyl]methoxy]pyridineYield 101.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 5-(3-hydroxy-3-methyl-1-butynyl)-3-(1-methyl-2(S) -pyrrolidinylmethoxy)pyridine (70 mg, 0.25 mmol) in toluene (3 mL) was added NaH (60% in mineral oil, 2 mg, 0.05 mmol). The reaction mixture was refluxed for 1 h, and then some toluene was distilled. After cooled, the mixture was treated with ice-cold water, and extracted with EtOAc (15 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by chromatography with CH2Cl2-MeOH (5:1) to give a light yellow oil (55 mg, 99%), [α]D−59 (c 1.4, CHCl3). 1H NMR (CDCl3) δ 8.32 (d, 1H, J=1.5 Hz), 8.29 (d, 1H, J=2.7 Hz), 7.28 (dd, 1H, J=2.7, 1.5 Hz), 4.01 (dd, 1H, J=9.3, 5.4 Hz), 3.93 (dd, 1H, J=9.3, 5.4 Hz), 3.20 (s, 1H), 3.16-3.09 (m, 1H), 2.73-2.63 (m, 1H), 2.48 (s, 3H), 2.32 (td, 1H, J=9.3, 7.2 Hz), 2.10-1.97 (m, 1H), 1.94-1.67 (m, 3H); 13C NMR (CDCl3) δ 154.38, 145.01, 138.27, 123.50, 119.26, 80.27, 71.12, 64.03, 57.67, 41.65, 28.47, 23.01.

Workup

  1. temperatureThe reaction mixture was refluxed for 1 h
  2. distillationsome toluene was distilled
  3. temperatureAfter cooled
  4. additionthe mixture was treated with ice-cold water
  5. extractionextracted with EtOAc (15 mL×3)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography with CH2Cl2-MeOH (5:1)

Sources & evidence

ORD record
ord-27044b5da5b44517b8f9697c4dd7adf4
Source dataset
uspto-grants-2011_10
Patent number
US08030300B2

Reaction notes

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