Methyl Ethyl Ketone → Anisole

HRID 930795Notes

Reaction equation

HRID 930795 reaction equation
[C:1]([O:4][CH2:5][CH3:6])(=[O:3])[CH3:2].O1CCC[CH2:8]1.[CH2:12]([C:16](C)=O)[CH:13](C)[CH3:14].C(C(C)=O)C>CC(C)=O.C(OC)(C)(C)C.O1CCOCC1.C(#N)C.C(O)C.CO.[N+](C)([O-])=O>[C:1]([O:4][CH:5]([CH3:8])[CH3:6])(=[O:3])[CH3:2].[C:5]1([O:4][CH3:1])[CH:6]=[CH:14][CH:13]=[CH:12][CH:16]=1

Participants

13

Reactant 4

HCID 6569Methyl Ethyl KetoneHCID 7909Methyl Isobutyl KetoneHCID 8028TetrahydrofuranHCID 8857Ethyl Acetate

Product 2

HCID 7519AnisoleHCID 7915Isopropyl Acetate

Reagents, catalysts & solvents 7

HCID 180AcetoneSolventHCID 702EthanolSolventHCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6375NitromethaneSolventHCID 15413tert-Butyl methyl etherSolventHCID 312751,4-DioxaneSolvent

Procedure

In some embodiments, the crystalline Form A has an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1. In some embodiments, the crystalline Form A has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.7±0.1° 2-Theta, 13.6±0.1° 2-Theta, 16.1±0.1° 2-Theta, 18.9±0.1° 2-Theta, 21.3±0.1° 2-Theta, and 21.6±0.1° 2-Theta. In some embodiments, the crystalline Form A has substantially the same X-ray powder diffraction (XRPD) pattern post storage at 40° C. and 75% RH for at least a week. In some embodiments, the crystalline Form A has substantially the same X-ray powder diffraction (XRPD) pattern post storage at 25° C. and 97% RH for at least a week. In some embodiments, the crystalline Form A has an Infrared (IR) spectrum substantially similar to the one set forth in FIG. 2. In some embodiments, the crystalline Form A has an Infrared (IR) spectrum weak peaks at about 1584 cm−1, about 1240 cm−1, about 1147 cm−1, about 1134 cm−1, about 1099 cm−1, and about 1067 cm−1. In some embodiments, the crystalline Form A has a melting temperature of about 155-156° C. In some embodiments, the crystalline Form A has a DSC thermogram substantially similar to the one set forth in FIG. 3. In some embodiments, the crystalline Form A has a thermo-gravimetric analysis (TGA) thermogram substantially similar to the one set forth in FIG. 4. In some embodiments, the crystalline Form A has a DSC thermogram with an endotherm having an onset at about 154° C. and a peak at about 157° C. and an exotherm at about 159° C. In some embodiments, the crystalline Form A is non-hygroscopic. In some embodiments, the crystalline Form A has an observed aqueous solubility of about 0.013 mg/mL at about pH 8. In some embodiments, the crystalline Form A that is characterized as having properties (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), and (k). In some embodiments, the crystalline Form A was obtained from ethyl acetate, isopropyl acetate, tetrahydrofuran, methyl isobutyl ketone (MIBK), methyl ethyl ketone (MEK), nitromethane, methanol, ethanol, acetonitrile, dioxane, methyl tert-butyl ether (MTBE), anisole, acetone, heptanes, a methanol/water mixture or an acetone/heptane mixture. In some embodiments, the crystalline Form A was obtained from a methanol/water mixture. In some embodiments, the crystalline Form A is unsolvated. In some embodiments, the crystalline Form A is anhydrous.

Workup

  1. customat 5.7±0.1°
  2. custom13.6±0.1°
  3. custom16.1±0.1°
  4. custom18.9±0.1°
  5. custom21.3±0.1°
  6. custom21.6±0.1°
  7. customat 40° C.
  8. wait75% RH for at least a week
  9. customat 25° C.
  10. wait97% RH for at least a week
  11. customat about 154° C.
  12. customat about 157° C.
  13. customat about 159° C

Sources & evidence

ORD record
ord-7b7178cbebc645e0a8ab11b78f16234a
Source dataset
uspto-grants-2016_03
Patent number
US09296753B2

Reaction notes

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