Hydrochloric Acid → 3-{[5-(Trifluoromethyl)pyridin-2-yl]oxy}propan-1-ol

HRID 1356966Notes

Reaction equation

HRID 1356966 reaction equation
[CH2:1]([OH:5])[CH2:2][CH2:3][OH:4].[H-].[Na+].Cl[C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][N:10]=1.Cl>CCCCCC.CN(C=O)C>[OH:4][CH2:3][CH2:2][CH2:1][O:5][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][N:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 104421,3-PropanediolHCID 24758Sodium hydrideHCID 923422-Chloro-5-(trifluoromethyl)pyridine

Product 1

HCID 112067993-{[5-(Trifluoromethyl)pyridin-2-yl]oxy}propan-1-olYield 43.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Procedure

A mixture of 12.6 g of 1,3-propanediol and 100 ml of N,N-dimethylformamide was stirred under a nitrogen stream, to which 3.30 g of an oily mixture containing 60% sodium hydride was added in small portions at room temperature over 30 minutes. After further stirring continued at room temperature for 1 hour, 20 ml of a DMF solution of 10.0 g of 2-chloro-5-trifluoromethylpyridine was added dropwise over 40 minutes. After further stirring continued under a nitrogen stream at room temperature overnight, 100 ml of about 2 N diluted hydrochloric acid was added over 15 minutes to stop the reaction. The reaction mixture was extracted twice with toluene at a total volume of 500 ml. The combined toluene layer was successively washed with diluted hydrochloric acid and aqueous sodium bicarbonate solution, dried with magnesium sulfate, and concentrated to obtain an oily product. The oily product was dissolved in 300 ml of hexane by heating, followed by recrystallization, which afforded 5.3 g of 2-(3-hydroxypropyloxy)-5-trifluoromethylpyridine as almost pure crystals (44% yield), m.p. 46.6° C.

Workup

  1. additionwas added in small portions at room temperature over 30 minutes
  2. stirringAfter further stirring
  3. stirringAfter further stirring
  4. customat room temperature
  5. additionwas added over 15 minutes
  6. customthe reaction
  7. extractionThe reaction mixture was extracted twice with toluene at a total volume of 500 ml
  8. washThe combined toluene layer was successively washed with diluted hydrochloric acid and aqueous sodium bicarbonate solution
  9. dry with materialdried with magnesium sulfate
  10. concentrationconcentrated
  11. customto obtain an oily product
  12. temperatureby heating
  13. customfollowed by recrystallization, which

Sources & evidence

ORD record
ord-9351e9e7bc534d208988faceb1afbb0a
Source dataset
uspto-grants-2003_07
Patent number
US06589914B2

Reaction notes

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