1,1'-Carbonyldiimidazole → (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-3-oxohexanoate

HRID 1056116Notes

Reaction equation

HRID 1056116 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[C:35]([O:41][CH2:42][CH3:43])(=[O:40])[CH2:36]C([O-])=O.[K+].[Cl-].[Mg+2].[Cl-]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH3:14])[C:10](=[O:12])[CH2:36][C:35]([O:41][CH2:42][CH3:43])=[O:40])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium ChlorideHCID 13273792(2S,3R)-2-{[(tert-butoxy)carbonyl]amino}-3-[(tert-butyldimethylsilyl)oxy]butanoic acid

Product 1

HCID 131736416(4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-3-oxohexanoateYield 81.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of (2S,3R)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)butanoic acid (614b) (1.01 g, 3.03 mmol) in THF (10 mL) was treated with 1,1′-carbonyldiimidazole (Aldrich) (0.59 g, 3.63 mmol) and heated at 60° C. for 2 h. A mixture of potassium ethyl malonate (Aldrich) (1.03 g, 6.06 mmol) and magnesium chloride (Aldrich) (0.58 g, 6.06 mmol) was added to the solution and heating was continued at 50° C. for 6 d. The suspension was extracted into EtOAc (2×100 mL) from saturated brine (100 mL) containing 1.0 M aq. HCl (25 mL). The combined organic extracts were washed with saturated aq. NaHCO3 (100 mL), back-extracting with EtOAc (100 mL). The organic extracts were dried (MgSO4) and concentrated to give (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-3-oxohexanoate (614) (995 mg, 2.46 mmol, 81% yield) as a pale yellow oil. LC-MS m/z 426.0, [M+Na]+.

Workup

  1. additionwas added to the solution
  2. temperatureheating
  3. extractionThe suspension was extracted into EtOAc (2×100 mL) from saturated brine (100 mL)
  4. additioncontaining 1.0 M aq. HCl (25 mL)
  5. washThe combined organic extracts were washed with saturated aq. NaHCO3 (100 mL)
  6. extractionback-extracting with EtOAc (100 mL)
  7. dry with materialThe organic extracts were dried (MgSO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-a179b4bb148d4ef1966c16ca75d6e17b
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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