3-Cyclopentylpropionyl chloride → (R)-3-(3-Cyclopentyl-1-oxopropyl)-(1-phenylmethyl)-2-oxazolidinone

HRID 30301

Reaction equation

HRID 30301 reaction equation
[C:1]1([CH2:7][C@@H:8]2[CH2:12][O:11][C:10](=[O:13])[NH:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[CH:19]1([CH2:24][CH2:25][C:26](Cl)=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]1>O1CCCC1>[CH:19]1([CH2:24][CH2:25][C:26]([N:9]2[C@H:8]([CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:12][O:11][C:10]2=[O:13])=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 660393-Cyclopentylpropionyl chlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinoneHCID 178418339Butyllithium

Product 1

HCID 2758003(R)-3-(3-Cyclopentyl-1-oxopropyl)-(1-phenylmethyl)-2-oxazolidinoneYield 54.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A dry round bottom flask was charged with of (R)-4-(phenylmethyl)-2-oxazolidinone (1, 17.7 g, 0.100 mol). Anhydrous tetrahydrofuran (300 mL) was then added, and the solution was cooled to −78° C. A solution of butyllithium (42.0 mL, 0.105 mol, 2.50 M in hexane) was added to the reaction flask over a 10-min period. After a few minutes, 3-Cyclopentylpropionyl chloride (16.8 mL, 0.110 mol) was added. The resulting solution was stirred for 30 min at −78° C., then allowed to warm to ambient temperature over a 30-min period. Excess 3-cyclopentylpropionyl chloride was quenched by the addition of 60 mL of saturated aqueous ammonium chloride. The bulk of the tetrahydrofuran and hexane was removed on a rotary evaporator, and the slurry was extricated with two 80 mL portion of dichloromethane. The combined organic layers were washed with 75 mL of 1 M sodium hydroxide and 75 mL of brine, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed under reduced pressure. The residue was triturated with hexane to provide 16.5 g of desired product 2 as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.18-7.40 (5 H, m), 4.67 (1 H, m), 4.12-4.22 (2 H, m), 3.30 (1 H, dd, J=13.4, 3.1 Hz), 2.84-3.06 (2 H, m), 2.76 (1 H, dd, J=13.4, 9.6 Hz), 1.42-1.96 (9 H, m), 1.15 (2 H, br, m).

Workup

  1. waitAfter a few minutes
  2. temperatureto warm to ambient temperature over a 30-min period
  3. customExcess 3-cyclopentylpropionyl chloride was quenched by the addition of 60 mL of saturated aqueous ammonium chloride
  4. customThe bulk of the tetrahydrofuran and hexane was removed on a rotary evaporator
  5. washThe combined organic layers were washed with 75 mL of 1 M sodium hydroxide and 75 mL of brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe solvent was removed under reduced pressure
  9. customThe residue was triturated with hexane

Sources & evidence

ORD record
ord-3b2fc9a261274b58bd8b58c8fb2a42e7
Source dataset
uspto-grants-2008_09
Patent number
US07423033B2

Linked notes

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