Water → Methanesulfonic Acid

HRID 587806Notes

Reaction equation

HRID 587806 reaction equation
[CH3:1][S:2]([OH:5])(=[O:4])=[O:3].O.[C:7]1([CH3:17])[CH:12]=[CH:11][C:10]([S:13]([OH:16])(=[O:15])=[O:14])=[CH:9][CH:8]=1.O>C(O)(C)C>[S:13]([C:10]1[CH:11]=[CH:12][C:7]([CH3:17])=[CH:8][CH:9]=1)([O-:16])(=[O:15])=[O:14].[CH3:1][S:2]([OH:5])(=[O:4])=[O:3]

Participants

6

Reactant 3

HCID 962Water2×HCID 6395Methanesulfonic AcidHCID 521998p-Toluenesulfonic acid monohydrate

Product 2

HCID 6395Methanesulfonic AcidHCID 85570p-Toluenesulfonate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Conditions

Temperature
22.5 °C

Procedure

To a 5-L 3-neck flask under an inert nitrogen atmosphere, 2.0 L of isopropanol (IPA) was charged. A slurry was prepared by adding 289 g of the amorphous free base of Compound 1 to the flask. A solution of p-toluenesulfonic acid hydrate (97.0 g) in IPA (400 mL) was then added to the slurry. The water content of the slurry supernatant was adjusted to 0.6 g/L with the addition of water (9 mL), and the slurry was stirred at 20-25° C. for 18 hours to produce a thick crystalline slurry. The slurry was filtered and washed with IPA (2×500 mL). Excess IPA was removed from the crystalline cake by blowing dry nitrogen through the cake for 24 hours. With the solids containing 3 weight-percent (wt %) of IPA, the cake was further dried by blowing humidified nitrogen through the cake at a relative humidity of 70-75% for 24 hours. The cake retained 0.9 wt % of IPA that was not further reduced by this method. Excess water was then removed from the cake by blowing dry nitrogen through the cake for 24 hours. The tosylate salt of Compound 1 was isolated as an orange powder (337 g). The isolated tosylate salt of Compound 1 was crystalline with only one observed form: a non-stoichiometric hemihydrate, as determined by x-ray powder diffraction (XPRD) and thermogravimetric (TG) analysis.

Workup

  1. customA slurry was prepared
  2. customto produce a thick crystalline slurry
  3. filtrationThe slurry was filtered
  4. washwashed with IPA (2×500 mL)
  5. customExcess IPA was removed from the crystalline cake
  6. customfor 24 hours
  7. additionWith the solids containing 3 weight-percent (wt %) of IPA
  8. customthe cake was further dried
  9. customfor 24 hours
  10. customExcess water was then removed from the cake
  11. customfor 24 hours

Sources & evidence

ORD record
ord-2f64339b53304139acd401dda6a9d1c1
Source dataset
uspto-grants-2016_01
Patent number
US09227921B2

Reaction notes

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