Methanol → HCID 131734584, compound

HRID 595281Notes

Reaction equation

HRID 595281 reaction equation
S(=O)(=O)(O)O.[OH:6][CH:7]([CH2:11][N:12]1[CH:16]=[C:15]([C:17]2[CH:22]=[C:21]([NH:23][C:24]3[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=3)[CH:20]=[C:19]([CH3:34])[CH:18]=2)[CH:14]=[N:13]1)[C:8]([OH:10])=[O:9].[CH3:35]O>O>[OH:6][C@H:7]([CH2:11][N:12]1[CH:16]=[C:15]([C:17]2[CH:22]=[C:21]([NH:23][C:24]3[N:29]=[C:28]([C:30]([F:31])([F:32])[F:33])[CH:27]=[CH:26][N:25]=3)[CH:20]=[C:19]([CH3:34])[CH:18]=2)[CH:14]=[N:13]1)[C:8]([O:10][CH3:35])=[O:9]

Participants

5

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 118208924HCID 118208924, compound

Product 1

HCID 131734584HCID 131734584, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

Sulfuric acid (0.10 ml, 1.83 mmol) was added to an oven-dried vial containing 2-hydroxy-3-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanoic acid (1.78 g, 1.83 mmol) in MeOH (12.2 ml) and the solution was warmed to 70° C. and stirred for 1 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0 to 80% EtOAc/hexanes) to afford racemic methyl (2R)-2-hydroxy-3-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanoate. The racemic sample was purified by super critical fluid chiral chromatography (AD-H 2.1×25 cm, 5 μm, 45%/55% 2-propanol/CO2, 70 mL/min, 12 min. run time, 220 nM) to afford (R or S) 2-methyl-2-hydroxy-3-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]propanoate (early eluting enantiomer). MS ESI calcd. for C19H19F3N5O3 [M+H]+ 422. found 422.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (0 to 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-33a9f7569fb84675bff102c8fb2d54be
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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