1,1'-Carbonyldiimidazole → tert-butyl (3S,5R)-3-{[(benzyloxy)carbonyl]amino}-5-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate

HRID 2192829Notes

Reaction equation

HRID 2192829 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15][C@H:14](C(O)=O)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:40]([O:42][C:43](=[O:48])[CH2:44][C:45]([K])=[O:46])[CH3:41].[Cl-].[Mg+2].[Cl-]>C1COCC1.Cl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:13][C@@H:14]([C:45](=[O:46])[CH2:44][C:43]([O:42][CH2:40][CH3:41])=[O:48])[CH2:15][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])[CH2:17]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 5360315Magnesium ChlorideHCID 59356597(3R,5S)-5-(benzyloxycarbonylamino)-1-tert-butoxycarbonyl-piperidine-3-carboxylic acidHCID 178472227HCID 178472227, compound

Product 1

HCID 59625444tert-butyl (3S,5R)-3-{[(benzyloxy)carbonyl]amino}-5-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylateYield 17.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3R,5S)-5-{[(benzyloxy)carbonyl]amino}-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (2.25 g) in THF (60 ml) was added 1,1′-carbonylbis(1H-imidazole) (1.20 g) and the mixture was stirred at room temperature for 2 hr. (3-Ethoxy-3-oxopropanoyl)potassium (1.26 g) and magnesium chloride (700 mg) were added and the reaction mixture was stirred with heating to reflux for 4 hr. After cooling to room temperature, the reaction mixture was diluted with 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed successively with 3.5 M aqueous potassium carbonate solution and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, eluted with ethyl acetate-hexane (10:90-80:20) and concentrated under reduced pressure to give the object compound (460 mg).

Workup

  1. stirringthe reaction mixture was stirred
  2. temperaturewith heating
  3. temperatureto reflux for 4 hr
  4. temperatureAfter cooling to room temperature
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed successively with 3.5 M aqueous potassium carbonate solution and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was evaporated under reduced pressure
  9. washeluted with ethyl acetate-hexane (10:90-80:20)
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b6b1608d561e4ce399452ac549f1fe16
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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