Water → 1,1-Dimethylethyl 1-ethyl-5-oxo-prolinate

HRID 554082Notes

Reaction equation

HRID 554082 reaction equation
[O:1]=[C:2]1[NH:6][C@H:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4][CH2:3]1.[H-].[Na+].[CH2:16](I)[CH3:17].O>O1CCCC1.C1(C)C=CC=CC=1>[CH2:16]([N:6]1[C:2](=[O:1])[CH2:3][CH2:4][C@H:5]1[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH3:17]

Participants

7

Reactant 4

HCID 962WaterHCID 6340Iodoethane2×HCID 24758Sodium hydride2×HCID 10888648tert-Butyl 5-oxo-L-prolinate

Product 1

HCID 674618121,1-Dimethylethyl 1-ethyl-5-oxo-prolinate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

1,1-dimethylethyl 5-oxo-L-prolinate (2.7 g, 12 mmol, prepared as described in Synth. Comm., 2005, 35(8), 1129) was added to a suspension of sodium hydride (0.428 g (60% suspension in oil), 10.7 mmol) in tetrahydrofuran (6 ml) and the mixture was stirred at room temperature for 5 minutes. Ethyl iodide (1.67 g, 10.7 mmol) was then added and the mixture was heated at 40° C. for 2 hrs. A further quantity of sodium hydride (0.24 g) was added and stirring continued overnight at room temperature. An additional quantity of ethyl iodide (0.86 ml) was added to the mixture at this stage and the mixture was left to stand at room temperature over the weekend. Water (˜10 ml) was added to the mixture and this was stirred for 15 minutes. The tetrahydrofuran was evaporated and the remaining aqueous layer was extracted with dichloromethane (2×50 ml) and a 3:1 mixture of chloroform and isopropanol (50 ml). The combined organic layers were filtered through a hydrophobic frit and evaporated to give a yellow oil. Toluene was added to the mixture and then evaporated to a yellow oil once more. This material was purified by automated silica flash-column chromatography (Biotage SP4), eluting with a 15-100% gradient of ethyl acetate in hexane, to give pure 1,1-dimethylethyl 1-ethyl-5-oxo-prolinate.

Workup

  1. temperaturethe mixture was heated at 40° C. for 2 hrs
  2. stirringstirring continued overnight at room temperature
  3. waitthe mixture was left
  4. customto stand at room temperature over the weekend
  5. stirringthis was stirred for 15 minutes
  6. customThe tetrahydrofuran was evaporated
  7. extractionthe remaining aqueous layer was extracted with dichloromethane (2×50 ml)
  8. additiona 3:1 mixture of chloroform and isopropanol (50 ml)
  9. filtrationThe combined organic layers were filtered through a hydrophobic frit
  10. customevaporated
  11. customto give a yellow oil
  12. customevaporated to a yellow oil once more
  13. customThis material was purified by automated silica flash-column chromatography (Biotage SP4)
  14. washeluting with a 15-100% gradient of ethyl acetate in hexane

Sources & evidence

ORD record
ord-69426acb1088434a8dc7bf946e08581f
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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