Reaktion #508778

Reaktionsgleichung

trimethyl phosphonoacetate

sodium hydride

(2S)-2-[(tert-butoxy)carbonylamino]-N-methoxy-N-methylpropanamide

lithium aluminum hydride

potassium hydrogen sulfate

→

title compound

Ausbeute 69.0%

Methyl (2E)(4S)-4-[(tert-butoxy)carbonylamino]pent-2-enoate

Ausbeute 69.0%

Lösungsmittel

brine

ethyl acetate

tetrahydrofuran

ethyl ether

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   ExtraktionThe resulting mixture was extracted three times with ethyl ether
2. 2
   WaschenThe combined organic layers were washed three times with 1N hydrogen chloride, three times with saturated aqueous sodium hydrogen carbonate
3. 3
   TrocknenThe solution was then dried over anhydrous sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Sonstigethe solvent evaporated
6. 6
   workup.DISSOLUTIONThe resulting solid was dissolved in anhydrous tetrahydrofuran (430 mL)
7. 7
   workup.STIRRINGhad been previously stirred at room temperature for 30 minutes
8. 8
   workup.STIRRINGThe reaction was stirred for 5 minutes in a ice water bath, at room temperature for 20 minutes
9. 9
   workup.STIRRINGstirred
10. 10
    Sonstigethe layers separated
11. 11
    TrocknenThe organic layer was dried over anhydrous sodium sulfate
12. 12
    Filtrationfiltered
13. 13
    Sonstigethe solvent evaporated
14. 14
    SonstigeThe resulting residue was purified by chromatography on a normal phase silica gel column with 0-30% ethyl acetate in hexanes
15. 15
    workup.ADDITIONFractions containing clean product
16. 16
    Sonstigethe solvent evaporated

Vorschrift

A solution of (2S)-2-[(tert-butoxy)carbonylamino]-N-methoxy-N-methylpropanamide (13.05 g, 56.18 mmol) in ethyl ether (560 mL) was chilled with an ice water bath and then 95% lithium aluminum hydride (2.80 g, 70.23 mmol) was added. The reaction was stirred at room temperature for 20 minutes and then a solution of aqueous potassium hydrogen sulfate (300 mL, 0.33M) was added. The resulting mixture was extracted three times with ethyl ether. The combined organic layers were washed three times with 1N hydrogen chloride, three times with saturated aqueous sodium hydrogen carbonate, and once with brine. The solution was then dried over anhydrous sodium sulfate, filtered, and the solvent evaporated. The resulting solid was dissolved in anhydrous tetrahydrofuran (430 mL) then added to a cold solution of trimethyl phosphonoacetate (27.3 mL, 168.5 mmol) and sodium hydride (112 mmol) in anhydrous tetrahydrofuran (130 mL) that had been previously stirred at room temperature for 30 minutes. The reaction was stirred for 5 minutes in a ice water bath, at room temperature for 20 minutes, and then water (500 mL) was added. The reaction mixture was diluted with brine and ethyl acetate, stirred, and the layers separated. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent evaporated. The resulting residue was purified by chromatography on a normal phase silica gel column with 0-30% ethyl acetate in hexanes. Fractions containing clean product were combined and the solvent evaporated to give the title compound (8.85 g, 69%): ES-MS (m/z) 230.4 [M+1]+.

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