Phosphate → 3-ethoxycarbonylmethyl-2,2-dimethyl-6-fluoro-2H-chromene

HRID 1032435Notes

Reaction equation

HRID 1032435 reaction equation
[CH3:1][C:2]1([CH3:14])[C:11](=O)[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([F:13])[CH:8]=2)[O:3]1.[H-].[Na+].[CH3:17][CH2:18][O:19][C:20]([CH2:22]P(OCC)(OCC)=O)=[O:21].P([O-])([O-])([O-])=O>O1CCCC1>[CH2:18]([O:19][C:20]([CH2:22][C:11]1[C:2]([CH3:14])([CH3:1])[O:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([F:13])=[CH:6][CH:5]=2)=[O:21])[CH3:17]

Participants

6

Reactant 4

HCID 1061PhosphateHCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 542615782,2-Dimethyl-6-fluoro-3-oxo-chroman

Product 1

HCID 540126573-ethoxycarbonylmethyl-2,2-dimethyl-6-fluoro-2H-chromene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

While stirring at from 0° to 5°, a solution of 5.7 g (29 mmol) of 2,2-dimethyl-6-fluoro-3-oxo-chroman in 100 ml of absolute tetrahydrofuran is added dropwise within a period of 30 minutes to a suspension of 1.69 g (35 mmol) of sodium hydride dispersion (55% in mineral oil), which has been substantially freed of mineral oil beforehand by repeated washing with n-hexane, in 100 ml of absolute tetrahydrofuran. The mixture is then stirred at from 0° to 5° for 30 minutes and then a solution of 7.9 g (35 mmol) of phosphonoacetic acid triethyl ester of the formula (H5C2O)2P(=O)CH2C(=O)OC2H5 in 70 ml of absolute tetrahydrofuran is added dropwise thereto within a period of 30 minutes at from 0° to 5°. The reaction mixture is stirred for a further 30 minutes at from 0° to 5° and then for 16 hours at room temperature and then poured into 700 ml of cold phosphate buffer solution (pH=6). The resulting mixture is extracted with diethyl ether. The combined organic phases are washed in succession with phosphate buffer solution (pH=7) and water, dried over sodium sulfate and concentrated by evaporation. The resulting red oil is chromatographed on 400 g of silica gel (0.040-0.063 mm) with toluene as eluant, yielding 5.76 g (75% of the theoretical yield) of 3-ethoxycarbonylmethyl-2,2-dimethyl-6-fluoro-2H-chromene in the form of an orange-coloured oil.

Workup

  1. washby repeated washing with n-hexane, in 100 ml of absolute tetrahydrofuran
  2. stirringThe mixture is then stirred at from 0° to 5° for 30 minutes
  3. stirringThe reaction mixture is stirred for a further 30 minutes at from 0° to 5°
  4. waitfor 16 hours at room temperature
  5. extractionThe resulting mixture is extracted with diethyl ether
  6. washThe combined organic phases are washed in succession with phosphate buffer solution (pH=7) and water
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated by evaporation
  9. customThe resulting red oil is chromatographed on 400 g of silica gel (0.040-0.063 mm) with toluene as eluant
  10. customyielding 5.76 g (75% of the

Sources & evidence

ORD record
ord-00cc7dd0b45f43989eb0fb5f89f28073
Source dataset
uspto-grants-1990_09
Patent number
US04957928

Reaction notes

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