Hydrochloric Acid → 3-(Methoxymethyl)-5-(pentafluoro-lambda6-sulphanyl)benzoic acid

HRID 1055687Notes

Reaction equation

HRID 1055687 reaction equation
[H-].[Na+].[OH:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1)[C:8]([OH:10])=[O:9].I[CH3:21].Cl>C1COCC1.O.CCCCC>[CH3:21][O:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([S:14]([F:19])([F:15])([F:16])([F:17])[F:18])[CH:13]=1)[C:8]([OH:10])=[O:9]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 896999933-(Hydroxymethyl)-5-(pentafluoro-lambda6-sulphanyl)benzoic acid

Product 1

HCID 897000823-(Methoxymethyl)-5-(pentafluoro-lambda6-sulphanyl)benzoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

108 mg (2.70 mmol) of sodium hydride (as a 60% strength suspension in mineral oil) were deoiled with pentane and then suspended in 5 ml of anhydrous THF. At 0° C., a solution of 250 mg (0.899 mmol) of the compound of Example 37A in 2.5 ml of anhydrous THF was slowly added dropwise to this suspension. After 30 min of stirring at 0° C., 170 μl (2.70 mmol) of iodomethane were added and the cooling bath was removed. Since, according to analytical HPLC, conversion was still incomplete after 6 h at RT, the mixture was once more cooled to 0° C., and a further 560 μl (9.0 mmol) of iodomethane and 36 mg (0.897 mmol) of sodium hydride (60% strength suspension in mineral oil) were added in succession. After 2 h of stirring at RT, about 75 ml of water were added carefully and the reaction mixture was acidified by addition of 1 M hydrochloric acid. The mixture was extracted three times with in each case about 25 ml of ethyl acetate. The combined organic extracts were washed successively with in each case about 30 ml of water and saturated sodium chloride solution. After drying over anhydrous magnesium sulphate, filtration and removal of the solvent on a rotary evaporator, the residue obtained was triturated with pentane. The crude product obtained in this manner was purified by preparative HPLC (Method 32). Pooling of the product fractions, removal of the solvent on a rotary evaporator and drying under high vacuum gave 153 mg (58% of theory) of the title compound.

Workup

  1. customthe cooling bath was removed
  2. waitwas still incomplete after 6 h at RT
  3. temperaturethe mixture was once more cooled to 0° C.
  4. stirringAfter 2 h of stirring at RT
  5. extractionThe mixture was extracted three times with in each case about 25 ml of ethyl acetate
  6. washThe combined organic extracts were washed successively with in each case about 30 ml of water and saturated sodium chloride solution
  7. dry with materialAfter drying over anhydrous magnesium sulphate, filtration and removal of the solvent on a rotary evaporator
  8. customthe residue obtained
  9. customwas triturated with pentane
  10. customThe crude product obtained in this manner
  11. customwas purified by preparative HPLC (Method 32)
  12. customPooling of the product fractions, removal of the solvent
  13. customon a rotary evaporator
  14. customdrying under high vacuum

Sources & evidence

ORD record
ord-77c5bdf55fbf4239ab932441887cc3c3
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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