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

HRID 885512Notes

Reaction equation

HRID 885512 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

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 after which LiCl (0.092 g, 2.179 mmol) and (R)-4-benzyloxazolidin-2-one (0.375 g, 2.116 mmol) were added stepwise. After warming 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. additionwere added stepwise
  2. washwashed with saturated NaHCO3 solution and brine
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe product was isolated by Flash column chromatography (silica gel column)
  7. washeluting with 0-100% dichloromethane/hexanes

Sources & evidence

ORD record
ord-0ae150e4d9b1462fb22cf9a3308f150f
Source dataset
uspto-grants-2012_08
Patent number
US08242174B2

Reaction notes

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