Sodium hydride → 5-Ethynyl-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine

HRID 1489406

Reaction equation

HRID 1489406 reaction equation
O[C:2](C)(C#C)[CH2:3][C:4]1[CH:5]=[C:6]([CH:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:7]=[N:8][CH:9]=1.[H-].[Na+].C1(C)C=CC=CC=1.CC(C)=O>C1(C)C=CC=CC=1>[C:3]([C:4]1[CH:5]=[C:6]([CH:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:7]=[N:8][CH:9]=1)#[CH:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 196943235-(2-Hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridineHCID 20247278Toluene acetone

Product 1

HCID 196943285-Ethynyl-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridineYield 61.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

5-(2-Hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine (495 mg, 1.5 mmol) was dissolved in toluene (30 mL) and catalytic sodium hydride (10 mg) was added. The solution was heated until several milliliters of toluene-acetone mixture was removed by distillation. The mixture was cooled to 25° C. and water (20 mL) and ethyl acetate (40 mL) were added. The organic phase was separated and the aqueous layer extracted with ethyl acetate (2×40 mL) and the combined organic extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3) as eluant to afford 5-ethynyl-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine as an oil (250 mg, 61%). LRMS (EI) m/e 217 (M+ +H--isobutylene), 216 (M+ --isobutylene); 1H NMR (CDCl3, 300 MHz): δ 8.59 (b-s, 1H), 8.42 (d, J=1.5 Hz, 1H), 7.59 (b-s, 1H), 4.94 (b-m, 0.5H), 4.77 (b-m, 0.5H), 3.64 (b-m, 2H), 3.21 (s, 1H), 2.39 (m, 1H), 1.75-2.0 (b-m, 3H), 1.46 (s, 3H), 1.21 (s, 6H).

Workup

  1. customwas removed by distillation
  2. additionwater (20 mL) and ethyl acetate (40 mL) were added
  3. customThe organic phase was separated
  4. extractionthe aqueous layer extracted with ethyl acetate (2×40 mL)
  5. washthe combined organic extracts were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3) as eluant

Sources & evidence

ORD record
ord-1e68b347206f406aae1791ad7dca1030
Source dataset
uspto-grants-1997_10
Patent number
US05677459

Linked notes

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