beta-Alanine, ethyl ester, hydrochloride → Ethyl 4-(tert-butyldimethylsilyloxy)-3-(3-ethoxy-3-oxopropylamino)butanoate

HRID 1092796Notes

Reaction equation

HRID 1092796 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[Si:10]([O:17][CH2:18]/[CH:19]=[CH:20]/[C:21]([O:23][CH2:24][CH3:25])=[O:22])([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].Cl.NCCC(O)=O>C(O)C>[Si:10]([O:17][CH2:18][CH:19]([NH:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 10490523(E)-4-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-2-butenoic Acid Ethyl EsterHCID 12201475beta-Alanine Hydrochloride

Product 1

HCID 86761499Ethyl 4-(tert-butyldimethylsilyloxy)-3-(3-ethoxy-3-oxopropylamino)butanoateYield 76%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 3-aminopropanoate HCl salt (4.6 g, 39.2 mmol, 1.4 eq) was added to a solution of (E)-ethyl 4-(tert-butyldimethylsilyloxy)but-2-enoate in 50 mL of ethanol. The mixture was stirred at RT overnight and then heated to reflux overnight. Another 9.2 g of 3-aminopropanoate HCl salt was added. The reaction was continued to heat at reflux for 2 hr. Solvents were removed; the yellow oily residue was dissolved in DCM, filtered through a pad of SiO2 (˜80 g), and washed with 800 mL EtOAc. The filtrate was concentrated to give the product 7.8 g (76%) as a light yellow liquid. HPLC retention time: T=1.844 min (analytical-3); ESI-MS:m/z 362.3 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. temperatureto heat
  4. temperatureat reflux for 2 hr
  5. customSolvents were removed
  6. dissolutionthe yellow oily residue was dissolved in DCM
  7. filtrationfiltered through a pad of SiO2 (˜80 g)
  8. washwashed with 800 mL EtOAc
  9. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-3fe8bf8bd6354c8693c5136b349ddfc2
Source dataset
uspto-grants-2012_03
Patent number
US08129538B1

Reaction notes

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