Citric Acid → HCID 66848062, compound

HRID 1631305Notes

Reaction equation

HRID 1631305 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:27]([F:30])([F:29])[F:28])=[C:6]([C@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([C:22]([O:24]CC)=[O:23])=[C:15]3[N:14]=2)[CH:7]=1.[OH-].[Na+].CO.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[Cl-].[Na+].O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:27]([F:30])([F:28])[F:29])=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]2[CH:18]=[CH:17][N:16]3[N:19]=[CH:20][C:21]([C:22]([OH:24])=[O:23])=[C:15]3[N:14]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 86664566HCID 86664566, compound

Product 1

HCID 66848062HCID 66848062, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

(R)-ethyl 5-(2-(5-fluoro-2-(trifluoromethyl)phenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (0.92 g, 2.2 mmol) was combined with 1N NaOH (25 mL) and MeOH (40 mL). The reaction mixture was stirred at ambient temperature for 20 hours, followed by heating to 40° C. until complete. Citric acid solid) was added until the mixture was pH 4-5. Brine (10 mL) was added and this was extracted with DCM and EtOAc. The combined organic layers were concentrated and the crude product was purified by reverse phase silica gel column chromatography eluting with 0-60% acetonitrile/water to yield 5-(2-(5-fluoro-2-(trifluoromethyl)phenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.45 g, 52%). MS (apci) m/z=395.0 (M+H).

Workup

  1. temperatureby heating to 40° C. until complete
  2. extractionthis was extracted with DCM and EtOAc
  3. concentrationThe combined organic layers were concentrated
  4. customthe crude product was purified by reverse phase silica gel column chromatography
  5. washeluting with 0-60% acetonitrile/water

Sources & evidence

ORD record
ord-fad4a83ce49c4cd2bde990e075a07db8
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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