Isopropanol → (S)-(-)-4-[4-[5-[(acetylamino)methyl]-2-oxo-3-oxazolidinyl]phenyl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid phenylmethyl ester

HRID 428740Notes

Reaction equation

HRID 428740 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:16][CH:15]=[C:14]([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][CH:18]=3)[CH2:13][CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[NH4+:36].[CH:37]([OH:40])(C)[CH3:38]>O1CCCC1.C(Cl)Cl>[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:16][CH:15]=[C:14]([C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:27][C@H:26]([CH2:28][NH:36][C:37](=[O:40])[CH3:38])[O:25][C:24]4=[O:34])=[CH:21][CH:22]=3)[CH2:13][CH2:12]2)=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 14923Ammonium HydroxideHCID 54108492(R)-(-)-3,6-Dihydro-4-[4-[5-[[(methylsulfonyl)oxy]methyl]-2-oxo-3-oxazolidinyl]phenyl]-1(2 H)-pyridinecarboxylic acid phenylmethyl ester

Product 1

HCID 54157116(S)-(-)-4-[4-[5-[(acetylamino)methyl]-2-oxo-3-oxazolidinyl]phenyl]-3,6-dihydro-1(2H)-pyridinecarboxylic acid phenylmethyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of (R)-(-)-3,6-dihydro-4-[4-[5-[[(methylsulfonyl)oxo]methyl]-2-oxo-3-oxazolidinyl]phenyl]-1(2 H)-pyridinecarboxylic acid phenylmethyl ester (EXAMPLE 17, Step 4, 935 mg) and concentrated aqueous ammonium hydroxide (4 mL) in isopropanol (4 mL) and tetrahydrofuran (4 mL) is placed in a sealed tube and immersed in an oil bath maintained at 95° C. for 18 hours. The mixture is then diluted with methylene chloride (40 mL), washed with saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the 5-aminomethyl-2-oxazolidinone intermediate (Rf=0.34 by TLC, methanol/chloroform, 10/90). A solution of this intermediate (783 mg) and pyridine (1.55 mL) in dry methylene chloride (19 mL) at 0° C. under N2 is treated with acetic anhydride (0.90 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 (20 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 get (230-400 mesh, 75 g), eluting with a gradient of methanol/methylene chloride (1/99-2/98). Pooling and concentration of those fractions with an Rf=0.26 by TLC (methanol/chloroform, 5/95) gives the title compound, mp 166-169° C.

Workup

  1. customis placed in a sealed tube
  2. customimmersed in an oil bath
  3. washwashed with saline (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f04f0810be454c2eb923dc5fa511e28a
Source dataset
uspto-grants-2001_11
Patent number
US06313307B1

Reaction notes

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