Citric Acid → tert-butyl [(1S,2R)-1-benzyl-2-(cyclopropylcarbonyl)-2-hydroxyethyl]carbamate

HRID 275627Notes

Reaction equation

HRID 275627 reaction equation
[CH:1]1(Br)[CH2:3][CH2:2]1.[Mg].[CH2:6]([C@H:13]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C@H:14]([C:16]#N)[OH:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:29]>CCOCC>[CH2:6]([C@H:13]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C@H:14]([C:16]([CH:1]1[CH2:3][CH2:2]1)=[O:29])[OH:15])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 78037BromocyclopropaneHCID 5462224MagnesiumHCID 13882350tert-butyl [(1S,2R)-1-benzyl-2-cyano-2-hydroxyethyl]carbamate

Product 1

HCID 86747482tert-butyl [(1S,2R)-1-benzyl-2-(cyclopropylcarbonyl)-2-hydroxyethyl]carbamate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

9.96 ml (124.5 mmol) of cyclopropyl bromide in 100 ml of ether were added dropwise within 30minutes to 3.03 g (124.5 mmol) of magnesium in 10 ml of abs. ether under slight reflux and the mixture was subsequently heated to reflux for 2 1/2 hours. Subsequently, 6.25 g (22.63 mmol) of tert-butyl [(1S,2R)-1-benzyl-2-cyano-2-hydroxyethyl]carbamate (EPA 0,266,950) were added dropwise thereto under reflux within 5 minutes and the mixture was heated to reflux for a further 2 1/2 hours. Finally, the mixture was left to cool (10°), 10% citric acid was added dropwise thereto and the mixture was extracted twice with ether. The organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulphate, filtered and evaporated under reduced pressure. Chromatography on silica gel using a 9:1 mixture of toluene and ethyl acetate yielded tert-butyl [(1S,2R)-1-benzyl-2-(cyclopropylcarbonyl)-2-hydroxyethyl]carbamate as a pale yellow solid, MS: 246 (M-C3H9O)+.

Workup

  1. temperaturethe mixture was subsequently heated
  2. temperatureto reflux for 2 1/2 hours
  3. temperatureunder reflux within 5 minutes
  4. temperaturethe mixture was heated
  5. temperatureto reflux for a further 2 1/2 hours
  6. waitFinally, the mixture was left
  7. additionwas added dropwise
  8. extractionthe mixture was extracted twice with ether
  9. washThe organic phase was washed with water and saturated sodium chloride solution
  10. dry with materialdried over magnesium sulphate
  11. filtrationfiltered
  12. customevaporated under reduced pressure
  13. additionChromatography on silica gel using a 9:1 mixture of toluene and ethyl acetate

Sources & evidence

ORD record
ord-68e33bf6e4da4c058c75861c1a5dfec2
Source dataset
uspto-grants-1995_02
Patent number
US05393875

Reaction notes

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