Tetrahydrofuran → HCID 66848275, compound

HRID 1671384Notes

Reaction equation

HRID 1671384 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.C([N-]C(C)C)(C)C.[Li+].[CH:27]1([C:32](Cl)=[O:33])[CH2:31][CH2:30][CH2:29][CH2:28]1>CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.CC(O)=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:32]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)=[O:33])[C:9]1=[O:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 78284Cyclopentanecarbonyl chlorideHCID 3790001-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl esterHCID 2724682Lithium diisopropylamide

Product 1

HCID 66848275HCID 66848275, compoundYield 42.7%

Reagents, catalysts & solvents 2

HCID 21899381Acetic acid--water (1/1)SolventHCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
-78 °C

Procedure

2-Oxopyrrolidine-1-carboxylic acid t-butyl ester (9.3 g, 50.4 mmol) was dissolved in THF (60 mL, 800 mmol) under nitrogen and was then cooled at −78° C. 2M Lithium diisopropylamide in heptane/THF/ethylbenzene (34 mL) was added over 40 minutes, and the resulting mixture was stirred for 1.5 hours at −78° C. Cyclopentanecarbonyl chloride (6.1 mL, 50 mmol) was dissolved in THF (4.0 mL, 49 mmol) and slowly added dropwise via syringe to the mixture over 30 minutes, then stirred at room temperature overnight. The reaction was quenched with saturated aqueous NH4Cl (50 mL) and the mixture stirred at room temperature for 30 minutes. The mixture was extracted with EtOAc (200 mL). The organic layer was washed with saturated aqueous NaHCO3 (2×75 mL), then saturated aqueous NaCl. The aqueous layers were combined and re-extracted with EtOAc (75 mL). The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was then placed on high vacuum for 10 minutes to yield a crude oil. The oil was dissolved in 50% AcOH/H2O and purified by preparative HPLC (10-70% MeCN/H2O; 0.05% TFA; over 80 minutes on a 2″ column at 40 mL/min). The fractions were collected and lyophilized to yield 3-cyclopentanecarbonyl-2-oxopyrrolidine-1-carboxylic acid t-butyl ester (6 g) as a yellow solid. MS m/z: [M+H]+ calcd for C15H23NO4, 281.3; found 282.2.

Workup

  1. additionslowly added dropwise via syringe to the mixture over 30 minutes
  2. stirringstirred at room temperature overnight
  3. customThe reaction was quenched with saturated aqueous NH4Cl (50 mL)
  4. stirringthe mixture stirred at room temperature for 30 minutes
  5. extractionThe mixture was extracted with EtOAc (200 mL)
  6. washThe organic layer was washed with saturated aqueous NaHCO3 (2×75 mL)
  7. extractionre-extracted with EtOAc (75 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. waitThe material was then placed on high vacuum for 10 minutes
  12. customto yield a crude oil
  13. custompurified by preparative HPLC (10-70% MeCN/H2O
  14. waitover 80 minutes on a 2″ column at 40 mL/min)
  15. customThe fractions were collected

Sources & evidence

ORD record
ord-09f9d5702b434f0bb70cc334768c395e
Source dataset
uspto-grants-2011_08
Patent number
US07994209B2

Reaction notes

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