Triethylamine → (4R,5S)-4-Methyl-3-(3-oxocyclohexanecarbonyl)-5-phenyloxazolidin-2-one

HRID 470591Notes

Reaction equation

HRID 470591 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]([OH:10])=O)[CH2:3]1.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[Li+].[Cl-].[CH3:27][C@@H:28]1[C@H:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:31][C:30](=[O:39])[NH:29]1>C1COCC1>[CH3:27][C@@H:28]1[C@H:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[O:31][C:30](=[O:39])[N:29]1[C:8]([CH:4]1[CH2:5][CH2:6][CH2:7][C:2](=[O:1])[CH2:3]1)=[O:10]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 433294Lithium ChlorideHCID 2733812(4R,5S)-(+)-4-Methyl-5-phenyl-2-oxazolidinoneHCID 27602523-Oxocyclohexane-1-carboxylic acid

Product 1

HCID 67510178(4R,5S)-4-Methyl-3-(3-oxocyclohexanecarbonyl)-5-phenyloxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

Racemic 3-oxocyclohexanecarboxylic acid (1.0 g, 7.03 mmol) was dissolved in THF (27.1 mL). To this solution was added triethylamine (1.9 mL, 13.5 mmol) followed by pivaloyl chloride (0.8 mL, 6.5 mmol) at −20° C. The resulting mixture was stirred at −20° C. for 1 h. After that, LiCl (0.252 g, 5.9 mmol) and (4R,5S)-4-methyl-5-phenyloxazolidin-2-one (0.959 g, 5.4 mmol) were added to the solution at −20° C. The reaction mixture was warmed to room temperature and stirred overnight, before the reaction was quenched with 0.2 N HCl. The THF was removed and the resulting mixture was partitioned by 0.2 N HCl and EtOAc. The organic layer was collected and washed with brine, dried (MgSO4) and concentrated. The resulting residue was purified by preparative HPLC (PHENOMENEX® Luna 5u C18 21.2×250 mm, isocratic elution with Method 1-MeOH/water containing 0.1% trifluoroacetic acid as defined above, 51% B over 30 min, 25 mL/min, 220 nM: the first peak (retention time=15.3 min) was (4R,5S)-4-methyl-3-((S)-3-oxocyclohexanecarbonyl)-5-phenyloxazolidin-2-one, Int-8A, (LCMS=302.0 [M+H]+), and the second peak (retention time=19.6 min) was (4R,5S)-4-methyl-3-((R)-3-oxocyclohexanecarbonyl)-5-phenyloxazolidin-2-one, Int-8B, LCMS=324.1 [M+Na]+ by comparison to the R-3-oxocyclohexanecarboxylic acid case (Aust. J. Chem., 34:2231 (1981)).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred overnight, before the reaction
  3. customwas quenched with 0.2 N HCl
  4. customThe THF was removed
  5. customthe resulting mixture was partitioned by 0.2 N HCl and EtOAc
  6. customThe organic layer was collected
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe resulting residue was purified by preparative HPLC (PHENOMENEX® Luna 5u
  11. washC18 21.2×250 mm, isocratic elution with Method 1-MeOH/water containing 0.1% trifluoroacetic acid
  12. customover 30 min

Sources & evidence

ORD record
ord-8b7ef1643e9843959f3159d9765c8f39
Source dataset
uspto-grants-2014_01
Patent number
US08629282B2

Reaction notes

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