1,1'-Carbonyldiimidazole → (S)-(-)-N-[[3-[4-[1-(Indole-2-carbonyl)-4-piperidinyl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 1276440Notes

Reaction equation

HRID 1276440 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[O:25]=[C:26]1[N:30]([C:31]2[CH:36]=[CH:35][C:34]([CH:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)=[C:33]([F:43])[CH:32]=2)[CH2:29][C@H:28]([CH2:44][NH:45][C:46](=[O:48])[CH3:47])[O:27]1>O1CCCC1>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([N:40]1[CH2:41][CH2:42][CH:37]([C:34]2[CH:35]=[CH:36][C:31]([N:30]3[CH2:29][C@H:28]([CH2:44][NH:45][C:46](=[O:48])[CH3:47])[O:27][C:26]3=[O:25])=[CH:32][C:33]=2[F:43])[CH2:38][CH2:39]1)=[O:12]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 72899Indole-2-carboxylic acidHCID 15887422(S)-(-)-N-[[2-Oxo-3-[4-(4-piperidinyl)-3-fluorophenyl]-5-oxazolidinyl]methyl]acetamide

Product 1

HCID 54177616(S)-(-)-N-[[3-[4-[1-(Indole-2-carbonyl)-4-piperidinyl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of indole-2-carboxylic acid (79 mg) and 1,1'-carbonyldiimidazole (80 mg) in dry tetrahydrofuran (2.0 mL) is stirred at ambient temperature for one hour, and a solution of (S)-(-)-N-[[2-oxo-3-[4-(4-piperidinyl)-3-fluorophenyl]-5-oxazolidinyl]methyl]acetamide (EXAMPLE 20, 150 mg) in dry tetrahydrofuran (6.0 mL) is added. The mixture is then stirred at ambient temperature for 19 hours, concentrated under reduced pressure, diluted with methylene chloride (20 mL), washed with saturated aqueous sodium bicarbonate (10 mL), water (10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced. pressure to give the crude product which is chromagraphed on silica gel (70-230 mesh, 10 g), eluting with methanol/methylene chloride (7.5/92.5). Pooling and concentration of those fractions with an Rf =0.67 by TLC (methanol/chloroform, 10/90) and recrystallization from chloroform/diethyl ether gives the title compound, mp 223-225° C.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additiondiluted with methylene chloride (20 mL)
  3. washwashed with saturated aqueous sodium bicarbonate (10 mL), water (10 mL) and saline (10 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced
  6. custompressure to give the crude product which
  7. washeluting with methanol/methylene chloride (7.5/92.5)
  8. customPooling and concentration of those fractions with an Rf =0.67 by TLC (methanol/chloroform, 10/90) and recrystallization from chloroform/diethyl ether

Sources & evidence

ORD record
ord-5f9c035d01904255aab26064ecb98336
Source dataset
uspto-grants-2000_12
Patent number
US06166056

Reaction notes

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