Sodium hydride → HCID 18391695, compound

HRID 617290Notes

Reaction equation

HRID 617290 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:17]1[CH:22]=[N:21][CH:20]=[CH:19][N:18]=1.S([O-])(O)(=O)=O.[K+]>O1CCCC1.C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:17]1[CH:22]=[N:21][CH:20]=[CH:19][N:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 24758Sodium hydride2×HCID 73277ChloropyrazineHCID 516920Potassium bisulfateHCID 10511797tert-butyl (2S)-2-(hydroxymethyl)azetidine-1-carboxylate

Product 1

HCID 18391695HCID 18391695, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

To an ice cooled solution of the compound of step 7b (941 mg, 5.0 mmol) in tetrahydrofuran (30 mL) under nitrogen, was added sodium hydride (80% dispersion in mineral oil, 180 mg, 7.5 mmol), portionwise. The reaction mixture stirred fifteen minutes followed by the dropwise addition of 2-chloropyrazine (590 mg, 5.1 mmol). The reaction was stirred 24 hours gradually warming to room temperature. Additional sodium hydride (40 mg) was added and stirring at room temperature continued until complete disappearance of starting material by TLC. The reaction mixture was then treated with a 10% aqueous solution of potassium hydrogen sulfate (20 ml) and the volatiles evaporated in vacuo. The mixture was then diluted with ethyl acetate (50 ml) and the organic phase was washed with saturated sodium hydrogen carbonate (2×20 ml). The organic phase was then dried (MgSO4), filtered and concentrated in vacuo. The resultant orange oil (1.37 g) was purified by flash silica gel chromatography (ethyl acetate:hexane=1:1), resulting in product isolated as an oil, in 80% yield (1.07 g). [α]23D =-62.8° (c 1.35, CHCl3). MS (CI/NH3) m/e 266 (M+H)+, 283 (M+NH4)+. 1H NMR (CDCl3, 300 MHz) δ: 8.28-8.27 (d, J=1.1 Hz, 1H), 8.13-8.12 (d, J=2.58 Hz, 1H), 8.08-8.06 (dd, J=2.58, J=1.5 Hz, 1H), 4.66-4.61 (dd, J=10.83, J=4.6, 1H), 4.58-4.51 (m, 1H), 4.50-4.45 (dd, J=10.83, J=3.13, 1H, 3.92-3.87 (dd, J=8.3, J=6.25, 2H), 2.41-2.29 (m, 1H), 2.26-2.16 (m, 1H), 1.41 (s, 9H).

Workup

  1. stirringThe reaction was stirred 24 hours
  2. stirringstirring at room temperature
  3. customthe volatiles evaporated in vacuo
  4. additionThe mixture was then diluted with ethyl acetate (50 ml)
  5. washthe organic phase was washed with saturated sodium hydrogen carbonate (2×20 ml)
  6. dry with materialThe organic phase was then dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resultant orange oil (1.37 g) was purified by flash silica gel chromatography (ethyl acetate:hexane=1:1)
  10. customresulting in product
  11. customisolated as an oil, in 80% yield (1.07 g)

Sources & evidence

ORD record
ord-1809ab39b4ae4a15bf12e97669e56e57
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Reaction notes

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