Triethylamine → (R)-3-(6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one

HRID 1158133Notes

Reaction equation

HRID 1158133 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=O)=[CH:4][C:3]=1[CH3:18].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[Li+].[Cl-].[CH2:35]([C@@H:42]1[CH2:46][O:45][C:44](=[O:47])[NH:43]1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>C1COCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([N:43]2[C@H:42]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:46][O:45][C:44]2=[O:47])=[O:15])=[CH:4][C:3]=1[CH3:18]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 433294Lithium ChlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinoneHCID 595125786-(4-Fluoro-3-methylbenzyloxy)hexanoic acid

Product 1

HCID 59512592(R)-3-(6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-oneYield 55.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

To a cooled (−10° C.) solution of 6-(4-fluoro-3-methylbenzyloxy)hexanoic acid (0.565 g, 2.222 mmol) in 15 mL of THF, were added stepwise triethylamine (0.80 mL, 5.713 mmol) and pivaloyl chloride (0.27 mL, 2.179 mmol). The reaction mixture was stirred at −10° C. for 1 h and then LiCl (0.092 g, 2.179 mmol) and (R)-4-benzyloxazolidin-2-one (0.375 g, 2.116 mmol) were added stepwise. After warmed slowly to room temperature with stirring overnight, the reaction mixture was diluted with ethyl acetate (80 mL) and washed with saturated NaHCO3 solution and brine. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (0.482 g, 52% yield). LC-MS: tR=11.2 min; m/z 414 (M+H)+.

Workup

  1. temperatureAfter warmed slowly to room temperature
  2. stirringwith stirring overnight
  3. washwashed with saturated NaHCO3 solution and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe product was isolated by Flash column chromatography (silica gel column)
  8. washeluting with 0-100% dichloromethane/hexanes

Sources & evidence

ORD record
ord-bfc1817be6f34a7183fe372658141f07
Source dataset
uspto-grants-2010_10
Patent number
US07807720B2

Reaction notes

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