Hydrochloric Acid → 5-Cyclopropyl-6-((R)-3-hydroxy-1-trifluoromethyl-propoxy)-pyridine-2-carboxylic acid

HRID 927765Notes

Reaction equation

HRID 927765 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][C:3]=1[CH:11]1[CH2:13][CH2:12]1.[F:14][C:15]([F:22])([F:21])[C@H:16]([OH:20])[CH2:17][CH2:18][OH:19].CC(C)([O-])C.[K+].Cl>CN(C=O)C>[CH:11]1([C:3]2[CH:4]=[CH:5][C:6]([C:8]([OH:10])=[O:9])=[N:7][C:2]=2[O:20][C@@H:16]([C:15]([F:22])([F:21])[F:14])[CH2:17][CH2:18][OH:19])[CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2779068(3R)-4,4,4-Trifluoro-1,3-butanediolHCID 23665647Potassium tert-butoxideHCID 866747936-Chloro-5-cyclopropyl-2-pyridinecarboxylic acid

Product 1

HCID 710876915-Cyclopropyl-6-((R)-3-hydroxy-1-trifluoromethyl-propoxy)-pyridine-2-carboxylic acidYield 7.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

6-Chloro-5-cyclopropyl-2-pyridinecarboxylic acid (CAN 1211530-95-8; 100 mg, 506 μmol), (R)-4,4,4-trifluorobutane-1,3-diol (219 mg, 1.52 mmol) and potassium tert-butoxide (114 mg, 1.01 mmol) were combined with DMF (2 mL) to give a white suspension. The reaction mixture was heated to 140° C. and stirred for 20 h. After cooling the mixture was poured into cold 1 M HCl (15 mL) and extracted with ethyl acetate (2×75 mL). The phases were combined, dried with Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC to give the title compound (12 mg, 7.8%) and its regioisomer; MS (EI) 304.2 (M+H)+.

Workup

  1. customto give a white suspension
  2. temperatureAfter cooling the mixture
  3. extractionextracted with ethyl acetate (2×75 mL)
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-21d787f463be48bbb7b7830ea6b46548
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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