Acetic Acid → tert-Butyl (4-fluoro-2-methoxypyridin-3-yl)carbamate

HRID 1898828Notes

Reaction equation

HRID 1898828 reaction equation
[CH3:1][O:2][C:3]1[C:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:7][CH:6]=[CH:5][N:4]=1.C([Li])(C)(C)C.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:32])(=O)=O)=CC=1.C(O)(=O)C>O1CCCC1.CCCCC.O.CCOCC>[F:32][C:7]1[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[C:8]=1[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 588007N-FluorobenzenesulfonimideHCID 11064075tert-Butyl (2-methoxypyridin-3-yl)carbamateHCID 178418306HCID 178418306, compound

Product 1

HCID 21464342tert-Butyl (4-fluoro-2-methoxypyridin-3-yl)carbamate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

To a solution of 8 g (35.7 mmol) of t-butyl N-(2-methoxy-3-pyridyl)carbamate in 200 mL of dry tetrahydrofuran was added with stirring at -60° C., 46.2 mL (78.5 mmol) of 1.7M t-butyl lithium in pentane. The resulting solution was allowed to warm slowly with stirring to -20° C. over a 20 to 30 min period. It was then cooled to about -60° C. and 12.2 g (38.7 mmol) of N-fluorodibenzenesulfonimide was added with stirring all at once. The mixture was allowed to warm to -20° C. and was poured into 500 mL of ether. The resulting ethereal solution was washed with a mixture of 2.5 g (41.7 mmol) of acetic acid and 150 mL of water. The aqueous phase was extracted with 200 mL of ether. The ethereal extracts were combined, dried over magnesium sulfate, filtered, and concentrated by evaporation. The residue was purified by flash chromatography to obtain 6.7 g (77 percent of theory) of the title compound as a colorless solid melting at 75°-77° C.

Workup

  1. temperatureto warm slowly
  2. stirringwith stirring to -20° C. over a 20 to 30 min period
  3. temperatureIt was then cooled to about -60° C.
  4. stirringwith stirring all at once
  5. temperatureto warm to -20° C.
  6. extractionThe aqueous phase was extracted with 200 mL of ether
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by evaporation
  10. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-14ef6c6852304eccbc5752bcf5d609eb
Source dataset
uspto-grants-1996_11
Patent number
US05571775

Reaction notes

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