Dimethyl methylphosphonate → Dimethyl(4-((tert-butyldimethylsilyl)oxy)-2-oxoheptyl)phosphonate

HRID 628931Notes

Reaction equation

HRID 628931 reaction equation
C([Li])CCC.[CH3:6][P:7](=[O:12])([O:10][CH3:11])[O:8][CH3:9].[Si:13]([O:20][CH:21]([CH2:28][CH2:29][CH3:30])[CH2:22][C:23](OCC)=[O:24])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>C1COCC1>[CH3:9][O:8][P:7]([CH2:6][C:23](=[O:24])[CH2:22][CH:21]([O:20][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:14])[CH3:15])[CH2:28][CH2:29][CH3:30])(=[O:12])[O:10][CH3:11]

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 14264095Ethyl 3-((tert-butyldimethylsilyl)oxy)hexanoateHCID 178418339Butyllithium

Product 1

HCID 131735358Dimethyl(4-((tert-butyldimethylsilyl)oxy)-2-oxoheptyl)phosphonateYield 36.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

n-Butyllithium (6.8 mL of a 1.6M solution in THF, 10.94 mmol) was added to a solution of dimethyl methylphosphonate (1.2 mL, 10.94 mmol) in THF (22 mL) at −78° C. After 0.5 h a solution of the ester 2 (2.0 g, 7.29 mmol) in THF (4 mL) was added. The reaction solution was allowed to warm to room temperature overnight on its own accord. After 16 h the reaction was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The organic portion was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 2:1 hex/EtOAc followed by 1:1 hex/EtOAc) afforded 0.93 g (36%) of phosphonate 3 (see Scheme 1).

Workup

  1. customAfter 16 h the reaction was quenched with saturated aqueous ammonium chloride
  2. extractionextracted with EtOAc
  3. washThe organic portion was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (silica gel, 2:1 hex/EtOAc followed by 1:1 hex/EtOAc)

Sources & evidence

ORD record
ord-9131a0a39fe546ef82b4f40a0381779a
Source dataset
uspto-grants-2016_04
Patent number
US09315486B2

Reaction notes

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