Acetic Acid → (S)-(-)-N-[[3-[4-[1-(4-Oxo-2-thiazolinyl)-4-piperidinyl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 428780Notes

Reaction equation

HRID 428780 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[C:9]([F:19])[CH:8]=2)[CH2:5][C@H:4]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:3]1.[S:25]([CH2:28][C:29]([O:31]C)=O)[C:26]#[N:27].C(O)(=O)C>C(O)C.C(Cl)Cl>[O:31]=[C:29]1[CH2:28][S:25][C:26]([N:16]2[CH2:15][CH2:14][CH:13]([C:10]3[CH:11]=[CH:12][C:7]([N:6]4[CH2:5][C@H:4]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:3][C:2]4=[O:1])=[CH:8][C:9]=3[F:19])[CH2:18][CH2:17]2)=[N:27]1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 12718Methyl 2-thiocyanatoacetateHCID 15887422(S)-(-)-N-[[2-Oxo-3-[4-(4-piperidinyl)-3-fluorophenyl]-5-oxazolidinyl]methyl]acetamide

Product 1

HCID 69765548(S)-(-)-N-[[3-[4-[1-(4-Oxo-2-thiazolinyl)-4-piperidinyl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-(−)-N-[[2-oxo-3-[4-(4-piperidinyl)-3-fluorophenyl]-5-oxazolidinyl]methyl]acetamide (EXAMPLE 20, 310 mg), methyl thiocyanatoacetate (121 mg, Bull. Chem. Soc. Jpn. 1972, 45(5), 1507) and glacial acetic acid (55 mg) in absolute ethanol (5 mL) is stirred at reflux under N2 for 4 hrs and then cooled to ambient temperature, diluted with methylene chloride (45 mL), washed with water (2×15 mL) and saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is chromatographed on silica gel (230-400 mesh, 45 g), eluting with methanol/methylene chloride (4/96), and those fractions with an Rf=0.47 by TLC (methanol/chloroform, (10/90) are pooled and concentrated to give the title compound, mp 222-224° C. (decomp.).

Workup

  1. temperatureat reflux under N2 for 4 hrs
  2. washwashed with water (2×15 mL) and saline (20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is chromatographed on silica gel (230-400 mesh, 45 g)
  6. washeluting with methanol/methylene chloride (4/96)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d6c14c1187cc4b938f7838e7ca574104
Source dataset
uspto-grants-2001_11
Patent number
US06313307B1

Reaction notes

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