HCID 54347376, compound → HCID 69766454, compound

HRID 277805Notes

Reaction equation

HRID 277805 reaction equation
CC([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:19]([F:20])=[CH:18][C:17]([N:21]3[CH2:25][C@H:24]([CH2:26][N:27]=[N+]=[N-])[O:23][C:22]3=[O:30])=[CH:16][C:15]=2[F:31])[CH2:10][CH2:9]1)=[O:7])(C)C>[Pd].CO>[C:14]1([CH2:11][O:5][C:6]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[C:19]([F:20])=[CH:18][C:17]([N:21]4[CH2:25][C@H:24]([CH2:26][NH:27][C:24](=[O:23])[CH3:25])[O:23][C:22]4=[O:30])=[CH:16][C:15]=3[F:31])[CH2:10][CH2:9]2)=[O:7])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

4

Reactant 1

HCID 54347376HCID 54347376, compound

Product 1

HCID 69766454HCID 69766454, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of (R)-(−)-4-[4-[5-(azidomethyl)-2-oxo-3-oxazolidinyl]-2,6-difluorophenyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester ((EXAMPLE 35, Step 6, 1.51 g) and 10% palladium on carbon (367 mg) in methanol (35 mL) is stirred under a hydrogen atmosphere (balloon) for 18 hours, the catalyst is removed by filtration through Celite and the filtrate is concentrated under reduced pressure to give the 5-aminomethyl-2-oxazolidinone intermediate (Rf=0.10 by TLC, methanol/chloroform, 5/95). A solution of this intermediate (1.28 g) and pyridine (2.51 mL) in dry methylene chloride (31 mL) at 0° C. under N2 is treated with acetic anhydride (1.47 mL), and the resulting solution is allowed to warm to ambient temperature with stirring over 1.5 hours. The mixture is then diluted with methylene chloride (15 mL), washed with water (10 mL), saturated aqueous sodium bicarbonate (2×10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product which is chromatographed on silica gel (70-230 mesh, 150 g), eluting with a gradient of methanol/methylene chloride (1/99-4/96). Pooling and concentration of those fractions with an Rf=0.31 by TLC (methanol/chloroform, 5/95), trituration with diethyl ether and filtration gives the title compound, NMR (CDCl13, 400 MHz) 7.06, 6.56, 4.78, 4.22, 4.00, 3.74, 3.65, 3.05, 2.75, 2.02, 1.96, 1.64, 1.47δ.

Workup

  1. customthe catalyst is removed by filtration through Celite
  2. concentrationthe filtrate is concentrated under reduced pressure

Sources & evidence

ORD record
ord-6508de335746412486bc4d4c6e56f1ab
Source dataset
uspto-grants-2002_03
Patent number
US06358942B1

Reaction notes

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