Triethylamine → Methyl 5-(benzyloxycarbonylamino)-3-oxopentanoate

HRID 2407041Notes

Reaction equation

HRID 2407041 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C:14]([OH:16])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][C:18]1(C)[O:23]C(=O)C[C:20](=O)[O:19]1.C(N(CC)CC)C.C(P(=O)(OCC)OCC)#N>C(Cl)Cl>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C:14](=[O:16])[CH2:17][C:18]([O:19][CH3:20])=[O:23])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 75313N-Benzyloxycarbonyl-beta-alanineHCID 76257Diethyl cyanophosphonate

Product 1

HCID 13541631Methyl 5-(benzyloxycarbonylamino)-3-oxopentanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-(Benzyloxycarbonylamino)propanoic acid [N-Cbz-β-alanine] (5.0 g, 22.4 mmoles) is suspended in methylene chloride (100 mL) and 2,2-dimethyl-1,3-dioxane-4,6-dione (3.3 g, 22.9 mmoles), triethylamine (8.5 mL, 61.0 mmoles) and diethyl cyanophosphonate (3.7 mL, 22.8 mmoles) are added. All solids dissolve quickly, and the reaction quickly turns yellow. The solution is stirred for 16 hours at ambient temperature. The reaction mixture is then diluted with methylene chloride (100 mL) and carefully washed three times with aqueous hydrochloric acid (3 M, 50 mL each), three times with water (50 mL each) and once with saturated aqueous sodium chloride (50 mL). The reaction mixture is then dried over anhydrous sodium sulfate, filtered and evaporated to an orange syrup. The syrup is dissolved in anhydrous methanol (200 mL) and heated to reflux for 16 hours. The methanol is evaporated and the crude product purified on silica gel (150 mL bed volume) eluting with methylene chloride (500 mL) then methylene chloride:methanol (99.5:0.5 [v/v], 500 mL then 99:1 [v/v], 1000 mL). Fractions containing pure product by thin layer chromatography are pooled and evaporated to a pale yellow oil. The oil is dried well in vacuo. The yield is 4.5 g (68%).

Workup

  1. dissolutionAll solids dissolve quickly
  2. customthe reaction quickly turns yellow
  3. washcarefully washed three times with aqueous hydrochloric acid (3 M, 50 mL each), three times with water (50 mL each)
  4. dry with materialThe reaction mixture is then dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated to an orange syrup
  7. dissolutionThe syrup is dissolved in anhydrous methanol (200 mL)
  8. temperatureheated
  9. temperatureto reflux for 16 hours
  10. customThe methanol is evaporated
  11. customthe crude product purified on silica gel (150 mL bed volume)
  12. washeluting with methylene chloride (500 mL)
  13. additionFractions containing pure product by thin layer chromatography
  14. customevaporated to a pale yellow oil
  15. customThe oil is dried well in vacuo

Sources & evidence

ORD record
ord-995e18a9fa62406393617909fadc619d
Source dataset
uspto-grants-2014_08
Patent number
US08809514B2

Reaction notes

Loading…