Sodium hydride → Boc-Asp vinyl phenyl sulfone

HRID 2168836Notes

Reaction equation

HRID 2168836 reaction equation
[H-].[Na+].[C:3]1([S:9]([CH2:12]P(=O)(OCC)OCC)(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[NH:21]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@H:22]([CH:31]=[O:32])[CH2:23][C:24](=[O:30])[O:25]C(C)(C)C.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[NH:21]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@H:22]([C:31]([OH:32])=[O:10])[CH2:23][C:24](=[O:30])[OH:25].[C:3]1([S:9]([CH:12]=[CH2:22])(=[O:10])=[O:11])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 10891636Diethyl ((phenylsulfonyl)methyl)phosphonateHCID 11716015tert-butyl (S)-3-((tert-butoxycarbonyl)amino)-4-oxobutanoate

Product 1

HCID 131731719Boc-Asp vinyl phenyl sulfone

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (40 mg (60%), 1.09 eq) was added to a solution of diethyl phenylsulfonylmethylphosphonate (0.279 g, 1.09 eq) in dry THF (5.6 ml) at O° C. The mixture was stirred for 20 minutes before adding, drop-wise, a solution of Boc-L-Asp(O-t-Bu)-H (0.24 g, 0.876 mmol) in 1.6 ml of THF. The mixture was stirred for 1.15 h at RT, then poured into a mix of ethyl acetate and ammonium chloride saturated solution (45/15 ml). The organic layer was dried over magnesium sulfate and the solvent was evaporated to dryness. The crude material was purified on silica gel (gradient: ethyl acetate/hexane) to make the desired compound with a high chemical yield.

Workup

  1. additionbefore adding
  2. stirringThe mixture was stirred for 1.15 h at RT
  3. additionpoured into
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. customthe solvent was evaporated to dryness
  6. customThe crude material was purified on silica gel (gradient: ethyl acetate/hexane)
  7. customyield

Sources & evidence

ORD record
ord-2ff4691da4a9414f852e2266d3a6f589
Source dataset
uspto-grants-2015_06
Patent number
US09045524B2

Reaction notes

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