Lithium → HCID 15481020, compound

HRID 428734Notes

Reaction equation

HRID 428734 reaction equation
[Li].[CH3:2][C:3]1([C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][C:9]=2[F:15])[CH2:6][NH:5][C:4]1=O>C1COCC1>[NH2:14][C:11]1[CH:12]=[CH:13][C:8]([C:3]2([CH3:2])[CH2:4][NH:5][CH2:6]2)=[C:9]([F:15])[CH:10]=1

Participants

4

Reactant 2

HCID 3028194LithiumHCID 15481019HCID 15481019, compound

Product 1

HCID 15481020HCID 15481020, compoundYield 106.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A flame-dried 3-neck 2-L round bottom flask equipped with mechanical stirrer, reflux condenser, and addition funnel was charged with 300 mL tetrahydrofuran and 350 mL 1M lithium aluminumhydride (0.35 mol) followed by cooling to 0° C. This solution was treated with a solution of 9.85 g 3-Methyl-3-(4-amino-2-fluorophenyl)-2-azetidinone (0.051 mol) in 210 mL THF with gas evolution and a yellow coloration. The cooling bath was removed and the reaction was heated to reflux with the rapid formation of a white precipitate. After 20 hours, the visually unchanged reaction mixture was cooled to room temperature and quenched by the successive addition of 13 mL water, 12 mL 5M sodium hydroxide, and 47 mL water. The resulting thick gelatinous suspension was diluted with one L ethyl acetate, filtered through a pad of CELITE, concentrated, and high vacuum dried to afford 9.82 g of the title compound as a light orange syrup. 1H NMR (300 MHz, CDCl3) δ 6.78 (t, 1H, J=8.5 Hz, aromatic), 6.37 (m, 2H, aromatic), 4.06 (d, 2H, J=8.2 Hz, N—CH2as), 3.81 (bs, 3H, NHs), 3.58 (d, 2H, J=8.2 Hz, N—CH2bs), 1.65 (s,3H, CH3).

Workup

  1. temperaturereflux
  2. additioncondenser, and addition funnel
  3. customThe cooling bath was removed
  4. temperaturethe reaction was heated
  5. temperatureto reflux with the rapid formation of a white precipitate
  6. temperaturethe visually unchanged reaction mixture was cooled to room temperature
  7. customquenched by the successive addition of 13 mL water, 12 mL 5M sodium hydroxide, and 47 mL water
  8. additionThe resulting thick gelatinous suspension was diluted with one L ethyl acetate
  9. filtrationfiltered through a pad of CELITE
  10. concentrationconcentrated
  11. customhigh vacuum dried

Sources & evidence

ORD record
ord-fecf093a3fe74238bb0e590d7d3d7c8f
Source dataset
uspto-grants-2001_11
Patent number
US06313307B1

Reaction notes

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