Imidazole → 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-phenylmethyldihydrofuran-2-(3H)one

HRID 1376656Notes

Reaction equation

HRID 1376656 reaction equation
N1C=CN=C1.[C:6]([Si](C)(C)Cl)([CH3:9])([CH3:8])[CH3:7].[C:14]([NH:21][C@@H:22]([CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@@H:23]([OH:36])[CH2:24][C@@H:25]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:26](O)=[O:27])([O:16]C(C)(C)C)=[O:15]>CN(C=O)C>[C:14]([NH:21][C@H:22]([C@H:23]1[O:36][C:26](=[O:27])[C@H:25]([CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:24]1)[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)([O:16][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:15]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 99791245(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid

Product 1

HCID 117320045(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-phenylmethyldihydrofuran-2-(3H)one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8 g of imidazole and 10 g of tert-butyldimethylchlorosilane are added, with stirring, to a solution of 6.35 g of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid in 90 ml of DMF. After being stirred for 18 hours at room temperature, the clear yellow solution is poured onto ice-water and extracted three times using 250 ml of ethyl acetate each time. The combined extracts are washed in succession three times with 10% citric acid, once with water, three times with aqueous saturated sodium hydrogen carbonate solution, once with water and finally with brine. After drying over sodium sulfate, the solvent is evaporated and the resulting tert-butyldimethylsilyl ether (13.5 g) is dissolved in 53 ml of THF and treated with 53 ml of acetic acid and 20 ml of water. After being stirred for 3 hours at room temperature, the mixture is poured onto water and extracted three times with ether. The combined ether extracts are washed twice with water and once with brine and dried over sodium sulfate. After concentration, the crude product is purified by column chromatography (SiO2, hexane/ethyl acetate: 3.5/1.5) and the title compound obtained. TLC Rf (D)=0.37; FAB-MS (M+H)+ =528.

Workup

  1. additionthe clear yellow solution is poured onto ice-water
  2. extractionextracted three times
  3. washThe combined extracts are washed in succession three times with 10% citric acid, once with water, three times with aqueous saturated sodium hydrogen carbonate solution, once with water and finally with brine
  4. dry with materialAfter drying over sodium sulfate
  5. customthe solvent is evaporated
  6. dissolutionthe resulting tert-butyldimethylsilyl ether (13.5 g) is dissolved in 53 ml of THF
  7. additiontreated with 53 ml of acetic acid and 20 ml of water
  8. stirringAfter being stirred for 3 hours at room temperature
  9. additionthe mixture is poured onto water
  10. extractionextracted three times with ether
  11. washThe combined ether extracts are washed twice with water and once with brine
  12. dry with materialdried over sodium sulfate
  13. concentrationAfter concentration
  14. customthe crude product is purified by column chromatography (SiO2, hexane/ethyl acetate: 3.5/1.5)

Sources & evidence

ORD record
ord-21aa3f9f13f6438eb579a9918d840c7e
Source dataset
uspto-grants-1997_09
Patent number
US05663168

Reaction notes

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