Pyridine → HCID 54376127, compound

HRID 428767Notes

Reaction equation

HRID 428767 reaction equation
C1(COC([N:11]2[CH2:16][CH2:15][C:14]([F:36])([C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:27][C@H:26]([CH2:28]OS(C)(=O)=O)[O:25][C:24]4=[O:34])=[CH:19][C:18]=3[F:35])[CH2:13][CH2:12]2)=O)C=CC=CC=1.[OH-].[NH4+].[N:39]1C=CC=[CH:41][CH:40]=1.C(OC(=O)C)(=[O:47])C>C(O)(C)C.C(#N)C.C(Cl)Cl>[O:34]=[C:24]1[N:23]([C:20]2[CH:21]=[CH:22][C:17]([C:14]3([F:36])[CH2:13][CH2:12][NH:11][CH2:16][CH2:15]3)=[C:18]([F:35])[CH:19]=2)[CH2:27][C@H:26]([CH2:28][NH:39][C:40](=[O:47])[CH3:41])[O:25]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 14923Ammonium HydroxideHCID 54361272HCID 54361272, compound

Product 1

HCID 54376127HCID 54376127, compound

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
95 °C

Procedure

A mixture of (R)-4-fluoro-4-[4-[5-[[(methylsulfonyl)oxy]methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperidinecarboxylic acid phenylmethyl ester (EXAMPLE 74, Step 4, 0.190 g) and concentrated aqueous ammonium hydroxide (2 mL) in isopropanol (1 mL) and acetonitrile (2 mL) is placed in a sealed tube and immersed in an oil bath maintained at 95° C. for 18 hrs. The mixture is then diluted with methylene chloride (20 mL), washed with water (10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude 5-aminomethyl-2-oxazolidinone intermediate (Rf=0.13 by TLC, methanol/chloroform, 5/95). A solution of this intermediate and pyridine (0.088 mL) in dry methylene chloride (3.6 mL) under N2 is treated with acetic anhydride (0.051 mL), and the resulting solution is stirred at ambient temperature for 18 hrs. The mixture is then diluted with methylene chloride (10 mL), washed with water (5 mL), saturated aqueous sodium bicarbonate (5 mL) and saline (5 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude acetamide intermediate which, after being combined with approx. 1.5 g of crude product from previous reaction workups, is chromatographed on silica gel (230-400 mesh, 150 g), eluting with a gradient of methanol/methylene chloride (1/9/90-1/4/95), and those fractions having an Rf=0.19 by TLC (triethylamine/methanol/chloroform, 1/9/90) are pooled and concentrated to give the title compound, mp 163-165° C.

Workup

  1. customis placed in a sealed tube
  2. customimmersed in an oil bath
  3. washwashed with water (10 mL) and saline (10 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude 5-aminomethyl-2-oxazolidinone intermediate (Rf=0.13 by TLC, methanol/chloroform, 5/95)
  7. washwashed with water (5 mL), saturated aqueous sodium bicarbonate (5 mL) and saline (5 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customto give the crude acetamide intermediate which
  11. customis chromatographed on silica gel (230-400 mesh, 150 g)
  12. washeluting with a gradient of methanol/methylene chloride (1/9/90-1/4/95)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-ea7f5f8050ad4c2cb5281fb45b5fd9ac
Source dataset
uspto-grants-2001_11
Patent number
US06313307B1

Reaction notes

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