Sodium hydride → tert-Butyl 3-(6-Nitropyridin-3-yloxy)azetidine-1-carboxylate

HRID 1919050Notes

Reaction equation

HRID 1919050 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][N:5]=1)([O-:3])=[O:2].I[CH:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1.[H-].[Na+]>CN(C=O)C>[N+:1]([C:4]1[N:5]=[CH:6][C:7]([O:10][CH:12]2[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15]2)=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27628576-Nitropyridin-3-olHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylate

Product 1

HCID 58043652tert-Butyl 3-(6-Nitropyridin-3-yloxy)azetidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 2-nitro-5-hydroxypyridine (2.00 g, 14.3 mmol), tert-butyl 3-iodoazetidine-1-carboxylate (6.06 g, 21.5 mmol), sodium hydride (800 mg, 20.2 mmol) and DMF (30 mL). The reaction mixture was heated at 110° C. for 24 h. After this time, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with ethyl acetate (200 mL) and washed with saturated aqueous sodium bicarbonate (100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford 251a in 95% yield (4.00 g) as a yellow oil: 1H NMR (500 MHz, CDCl3) d 8.27 (d, 1H, J=9.0 Hz), 8.14 (d, 1H, J=3.0 Hz), 7.26 (dd, 1H, J=9.0, 3.0 Hz), 5.04 (m, 1H), 4.39 (m, 2H), 4.06 (m, 2H), 1.44 (s, 9H); MS (ESI+) m/z 196.1 (M-Boc+H).

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. temperatureAfter this time, the reaction mixture was cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with ethyl acetate (200 mL)
  6. washwashed with saturated aqueous sodium bicarbonate (100 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-c9b3cbe3c6654cf2b6472ba4b98ebfe6
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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