4-[2-(2,4-Difluoro-phenyl)-1-methoxycarbonyl-2-oxo-ethylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester → 4-[5-(2,4-Difluoro-phenyl)-4-methoxycarbonyl-oxazol-2-yl]-piperidine-1-carboxylic acid benzyl ester

HRID 2288970Notes

Reaction equation

HRID 2288970 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=O)[NH:18][CH:19]([C:30]([O:32][CH3:33])=[O:31])[C:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[F:29])=[O:21])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>S(Cl)(Cl)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[O:21][C:20]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[F:29])=[C:19]([C:30]([O:32][CH3:33])=[O:31])[N:18]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 538667984-[2-(2,4-Difluoro-phenyl)-1-methoxycarbonyl-2-oxo-ethylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 544076884-[5-(2,4-Difluoro-phenyl)-4-methoxycarbonyl-oxazol-2-yl]-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

To a 1 liter round bottom flask fitted with a condenser, nitrogen inlet, and magnetic stir bar is added 4-[2-(2,4-Difluoro-phenyl)-1-methoxycarbonyl-2-oxo-ethylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester, (32 g, 67.4 mmol), and 120 mL of thionyl chloride. The mixture is immersed in an oil bath preheated to 70° C. and stirred for 10 minutes. The reaction is removed, cooled to room temperature and concentrated to an amber oil. The amber oil is carefully treated with about 50 g of ice, and 350 mL of saturated sodium bicarbonate. The resulting mixture is extracted with 3×100 mL of diethyl ether. The organic layers are combined, washed with brine, dried over magnesium sulfate and concentrated to a thick amber paste to yield the title compound.

Workup

  1. customTo a 1 liter round bottom flask fitted with a condenser, nitrogen inlet, and magnetic stir bar
  2. customThe mixture is immersed in an oil bath
  3. custompreheated to 70° C.
  4. customThe reaction is removed
  5. concentrationconcentrated to an amber oil
  6. additionThe amber oil is carefully treated with about 50 g of ice, and 350 mL of saturated sodium bicarbonate
  7. extractionThe resulting mixture is extracted with 3×100 mL of diethyl ether
  8. washwashed with brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated to a thick amber paste

Sources & evidence

ORD record
ord-9d433be785604e48ab9aaafe953d79ef
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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