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

HRID 632387Notes

Reaction equation

HRID 632387 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 103078691,3-Butanediol, 4,4,4-trifluoro-, (S)-HCID 23665647Potassium tert-butoxideHCID 866747936-Chloro-5-cyclopropyl-2-pyridinecarboxylic acid

Product 1

HCID 710872875-Cyclopropyl-6-((S)-3-hydroxy-1-trifluoromethyl-propoxy)-pyridine-2-carboxylic acidYield 5.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

6-Chloro-5-cyclopropyl-2-pyridinecarboxylic acid (CAN 1211530-95-8; 180 mg, 901 μmol), (S)-4,4,4-trifluorobutane-1,3-diol (394 mg, 2.73 mmol) and potassium tert-butoxide (307 mg, 2.73 mmol) were combined with DMF (3 mL) to give a white suspension. The reaction mixture was heated to 140° C. and stirred for 48 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 (15 mg, 5.4%) 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-a781ba4597ef41b3821c5578433b5a14
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Reaction notes

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