Dimethylformamide → [3-[[3-(2-ethoxy-2-oxoethyl)-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl ester

HRID 1069647Notes

Reaction equation

HRID 1069647 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([OH:15])[CH:13]=2)[NH:8][CH:7]=1)[CH3:2].CN(C=O)C.[H-].[Na+].[CH3:24][O:25][P:26]([CH2:30][CH2:31][CH2:32]Br)(=[O:29])[O:27][CH3:28]>C1COCC1.O.C(OCC)(=O)C>[CH3:24][O:25][P:26]([CH2:30][CH2:31][CH2:32][O:15][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:6][C:14]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH:7]=[C:6]2[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:16])(=[O:29])[O:27][CH3:28]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2834991-Bromo-3-dimethoxyphosphorylpropaneHCID 145733265-hydroxy-1H-indole-3-acetic acid ethyl ester

Product 1

HCID 10813793[3-[[3-(2-ethoxy-2-oxoethyl)-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl esterYield 142.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Hydroxy-1H-indole-3-acetic acid ethyl ester (560 mg. 1,8 mmol) was dissolved in 25 mL of THF and 75 mL of DMF and 80 mg (2.0 mmol) of 60% NaH/mineral oil added. After 0.17 hours, 465 mg (2.0 mmol) of (3-bromopropyl)phosphonic acid dimethyl ester was added and stirring maintained for 3.0 hours. The mixture was diluted with water and ethyl acetate, the organic layer separated, washed with water, brine and dried (Na2SO4). The solution was evaporated at reduced pressure and the residue chromatographed on florisil eluting with a gradient, 1% MeOH/methylene chloride→3% MeOH/methylene chloride, to give 590 mg (71% yield) of [3-[[3-(2-ethoxy-2-oxoethyl)-1-(phenylmethyl)-1H-indol-5-yl]oxy]propyl]phosphonic acid dimethyl ester.

Workup

  1. temperaturemaintained for 3.0 hours
  2. customthe organic layer separated
  3. washwashed with water, brine
  4. dry with materialdried (Na2SO4)
  5. customThe solution was evaporated at reduced pressure
  6. customthe residue chromatographed on florisil eluting with a gradient, 1% MeOH/methylene chloride→3% MeOH/methylene chloride

Sources & evidence

ORD record
ord-c55321114ca24f64b0eab6c86b701a5e
Source dataset
uspto-grants-2001_06
Patent number
US06252084B1

Reaction notes

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