Dimethyl methylphosphonate → (S)-tert-Butyl 1-(dimethoxyphosphoryl)-2-oxohex-5-en-3-ylcarbamate

HRID 1396329Notes

Reaction equation

HRID 1396329 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].C([Li])CCC.[C:13]([O:17][C:18]([NH:20][C@@H:21]([CH2:26][CH:27]=[CH2:28])[C:22](OC)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14]>C1COCC1>[CH3:4][O:3][P:2]([CH2:1][C:22](=[O:23])[C@@H:21]([NH:20][C:18](=[O:19])[O:17][C:13]([CH3:15])([CH3:14])[CH3:16])[CH2:26][CH:27]=[CH2:28])([O:5][CH3:6])=[O:7]

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 9837499(S)-Methyl 2-((tert-butoxycarbonyl)amino)pent-4-enoateHCID 178418339Butyllithium

Product 1

HCID 87132892(S)-tert-Butyl 1-(dimethoxyphosphoryl)-2-oxohex-5-en-3-ylcarbamateYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of dimethyl methylphosphonate (15.85 mL, 148 mmol) in THF (99 mL) at −78° C. was added n-butyllithium (93 mL, 148 mmol) slowly. After addition was completed, the reaction mixture was stirred for 30 min and then a solution of (S)-methyl 2-(tert-butoxycarbonylamino)pent-4-enoate (6.8 g, 29.7 mmol) in THF (15 mL) was added slowly. Stirring was continued for another 40 min at −78° C. The reaction was then quenched by adding water and diluted with EtOAc. The organic layer was washed with 1 M HCl, saturated NaHCO3 and brine. The organic layer was then dried over MgSO4, filtered and concentrated to give a clear oil. The crude product was then purified by silica gel chromatography to give the desired product (9.3 g, 98%) as colorless oil. MS (ESI) m/z: 599.0 (M+Na)+.

Workup

  1. additionAfter addition
  2. stirringStirring
  3. waitwas continued for another 40 min at −78° C
  4. customThe reaction was then quenched
  5. additionby adding water
  6. additiondiluted with EtOAc
  7. washThe organic layer was washed with 1 M HCl, saturated NaHCO3 and brine
  8. dry with materialThe organic layer was then dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a clear oil
  12. customThe crude product was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-84528276d75e42e4b747168cac28828f
Source dataset
uspto-grants-2014_12
Patent number
US08901115B2

Reaction notes

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