Hydrochloric Acid → 5-Cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid

HRID 1480100Notes

Reaction equation

HRID 1480100 reaction equation
Cl[C:2]1[C:7]([CH:8]2[CH2:10][CH2:9]2)=[CH:6][N:5]=[C:4]([C:11]([OH:13])=[O:12])[CH:3]=1.[F:14][C:15]([F:19])([F:18])[CH2:16][OH:17].[H-].[Na+].Cl>C(OC(=O)C)C>[CH:8]1([C:7]2[C:2]([O:17][CH2:16][C:15]([F:19])([F:18])[F:14])=[CH:3][C:4]([C:11]([OH:13])=[O:12])=[N:5][CH:6]=2)[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 902035204-Chloro-5-cyclopropylpicolinic acid

Product 1

HCID 902036745-Cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acidYield 47%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-Chloro-5-cyclopropyl-pyridine-2-carboxylic acid (Example 48b, 680 mg, 3.44 mmol) were added 2,2,2-trifluoroethanol (CAN 75-89-8, 1.03 g, 746 μl, 10.3 mmol) and sodium hydride 60% (551 mg, 13.8 mmol) by portions. The reaction mixture was stirred at room temperature for 30 min and then stirred at 120° C. for 18 h. The reaction mixture was cooled down, diluted with ethylacetate and poured in a separatory funnel. The mixture was extracted with an aqueous 4.0M solution hydrochloric acid (6.88 ml, 27.5 mmol). The organic phase was collected. The organic phase was dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a dichloromethane/methanol gradient to yield the title compound (420 mg, 47%) as light brown solid. MS (ESI, m/z): 260.2 (M−H+)

Workup

  1. stirringstirred at 120° C. for 18 h
  2. temperatureThe reaction mixture was cooled down
  3. additionpoured in a separatory funnel
  4. customThe organic phase was collected
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. customevaporated down to dryness
  7. customThe crude material was purified by flash chromatography on silica eluting with a dichloromethane/methanol gradient

Sources & evidence

ORD record
ord-f32956c5420243058b549aa970ed0ba8
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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