Diethyl (2-amino-2-oxoethyl)phosphonate → (2R,4R)-1-allyloxycarbonyl-4-tert-butyl-dimethylsilyloxy-2-[2-{4-(2-carbamoylethenyl)imidazol-1-yl}ethyl]pyrrolidine

HRID 975715Notes

Reaction equation

HRID 975715 reaction equation
[C:1]([CH2:4]P(=O)(OCC)OCC)(=[O:3])[NH2:2].CC(C)([O-])C.[K+].[CH2:19]([O:22][C:23]([N:25]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:26]1[CH2:38][CH2:39][N:40]1[CH:44]=[C:43]([CH:45]=O)[N:42]=[CH:41]1)=[O:24])[CH:20]=[CH2:21]>O1CCCC1.C(OCC)(=O)C.O>[CH2:19]([O:22][C:23]([N:25]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:36])([CH3:37])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:26]1[CH2:38][CH2:39][N:40]1[CH:44]=[C:43]([CH:45]=[CH:4][C:1](=[O:3])[NH2:2])[N:42]=[CH:41]1)=[O:24])[CH:20]=[CH2:21]

Participants

7

Reactant 3

HCID 225722Diethyl (2-amino-2-oxoethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 53740223(2R,4R)-1-allyloxycarbonyl-4-tert-butyldimethylsilyloxy-2-{2-(4-formylimidazol-1-yl)ethyl}pyrrolidine

Product 1

HCID 53721366(2R,4R)-1-allyloxycarbonyl-4-tert-butyl-dimethylsilyloxy-2-[2-{4-(2-carbamoylethenyl)imidazol-1-yl}ethyl]pyrrolidineYield 52.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of diethyl carbamoylmethylphosphonate (12.7 g) and potassium tert-butoxide (13.9 g) in tetrahydrofuran (400 ml) were added a solution of (2R,4R)-1-allyloxycarbonyl-4-tert-butyldimethylsilyloxy-2-{2-(4-formylimidazol-1-yl)ethyl}pyrrolidine (24 g) in tetrahydrofuran (50 ml) at 45° C. After stirring for 1 hour, to the reaction mixture were added water (3 ml). Evaporation of the solvent gave a residue, which was dissolved in a mixture of ethyl acetate (500 ml) and water (50 ml). The organic layer was separated, washed in turn with water (50 ml×2) and brine (50 ml×2), and dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (500 ml) eluting with a mixture of dichloromethane and methanol (10:1) to give (2R,4R)-1-allyloxycarbonyl-4-tert-butyl-dimethylsilyloxy-2-[2-{4-(2-carbamoylethenyl)imidazol-1-yl}ethyl]pyrrolidine (13.87 g).

Workup

  1. customEvaporation of the solvent
  2. customgave a residue, which
  3. customThe organic layer was separated
  4. washwashed in turn with water (50 ml×2) and brine (50 ml×2)
  5. dry with materialdried over magnesium sulfate
  6. customEvaporation of the solvent
  7. customgave an oil, which
  8. customwas chromatographed on silica gel (500 ml)
  9. washeluting with a mixture of dichloromethane and methanol (10:1)

Sources & evidence

ORD record
ord-e8f796a4a3b7445297b8a8c9f8917cfa
Source dataset
uspto-grants-1997_03
Patent number
US05608056

Reaction notes

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