Ethyl chloroformate → Ethyl 2-fluoro-6-pivaloylaminopyridine-3-carboxylate

HRID 1939244Notes

Reaction equation

HRID 1939244 reaction equation
[F:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH:5]=[CH:4][CH:3]=1.[Li]CCCC.Cl[C:21]([O:23][CH2:24][CH3:25])=[O:22].C(NC1C(C([O-])=O)=CC=C(F)N=1)(=O)C(C)(C)C>C1COCC1.O>[F:1][C:2]1[C:3]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:4][CH:5]=[C:6]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])[N:7]=1

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 13154251HCID 13154251, compoundHCID 214672542-Pivaloylamino-6-fluoropyridine-3-carboxylateHCID 178418339Butyllithium

Product 1

HCID 15893123Ethyl 2-fluoro-6-pivaloylaminopyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-fluoro-2-pivaloylaminopyridine (2 g) in THF (30 ml) was cooled to -78° C. and BuLi (15 mL of 1.6M in hexane) was added and the reaction stirred at 0° C. for 2 h. On re-cooling to -78° C., ethyl chloroformate (2 mL) was added and the reaction allowed to warm slowly to room temperature over 1 h. Water (10 ml) was added and the products extracted into Et2O (3×50 ml) and dried (Na2 SO4). Concentration afforded an oil which was triturated with petrol to give a solid, the isomeric 2-pivaloylamino-6-fluoropyridine-3-carboxylate (1H NMR [CDCl3 ] δ1.36 (s, 9H), 1.43 (t, 3H), 4.41 (q, 2H), 6.64 (dd, 1H), 8.45 (t, 1H), 11.34 (brs, 1H). The mother liquors were concentrated and purified by flash column chromatography (SiO2, Petrol to 5% Et2O/petrol to give ethyl 2-fluoro-6-pivaloylaminopyridine-3-carboxylate (1.2 g).

Workup

  1. temperatureOn re-cooling to -78° C.
  2. temperatureto warm slowly to room temperature over 1 h
  3. extractionthe products extracted into Et2O (3×50 ml)
  4. customdried (Na2 SO4)
  5. concentrationConcentration
  6. customafforded an oil which
  7. customwas triturated with petrol
  8. customto give a solid
  9. concentrationThe mother liquors were concentrated
  10. custompurified by flash column chromatography (SiO2, Petrol to 5% Et2O/petrol

Sources & evidence

ORD record
ord-27a579a0eb4e466c81679da4fc175b9c
Source dataset
uspto-grants-1997_12
Patent number
US05696129

Reaction notes

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