Hydrochloric Acid → (2-Chloropyridin-4-yl)methanol

HRID 1165762Notes

Reaction equation

HRID 1165762 reaction equation
[BH4-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([C:10](O)=[O:11])[CH:7]=[CH:6][N:5]=1.[H][H].B(F)(F)F.CCOCC.Cl>O1CCCC1>[Cl:3][C:4]1[CH:9]=[C:8]([CH2:10][OH:11])[CH:7]=[CH:6][N:5]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8000Boron trifluoride etherateHCID 2369852-Chloroisonicotinic acidHCID 4311764Sodium borohydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 7062237(2-Chloropyridin-4-yl)methanolYield 83.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

35.59 g of sodium borohydride was suspended in 3 liters of tetrahydrofuran, and the suspension was stirred by a mechanical stirrer. The suspension was cooled with ice water, and 98.83 g of 2-chloro-4-pyridinecarboxylic acid was added little by little. The mixture was heated to room temperature, and stirred until evolution of hydrogen ceased. A solution of 148 ml of boron trifluoride etherate in 1000 ml of tetrahydrofuran was added dropwise at room temperature for 3 hours. After the addition, the mixture was stirred for 20 hours. The reaction solution was cooled with ice water, and adjusted to pH 1 to 2 with 1.5N hydrochloric acid. The tetrahydrofuran was evaporated under reduced pressure, and a 4N aqueous solution of sodium hydroxide was added to adjust the pH of the mixture to 10 to 11. The solution was then extracted with ethyl acetate and the organic layer was washed with a saturated aqueous solution of sodium chloride. The aqueous layer was further extracted with ethyl acetate twice, and the organic layers were washed with a saturated aqueous solution of sodium chloride. The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give 75.0 g (yield 83%) of 2-chloro-4-pyridinemethanol.

Workup

  1. additionwas added little by little
  2. additionAfter the addition
  3. stirringthe mixture was stirred for 20 hours
  4. customThe tetrahydrofuran was evaporated under reduced pressure
  5. additiona 4N aqueous solution of sodium hydroxide was added
  6. extractionThe solution was then extracted with ethyl acetate
  7. washthe organic layer was washed with a saturated aqueous solution of sodium chloride
  8. extractionThe aqueous layer was further extracted with ethyl acetate twice
  9. washthe organic layers were washed with a saturated aqueous solution of sodium chloride
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8d47daa573a94d1ca2cad59d7d467d0e
Source dataset
uspto-grants-1990_03
Patent number
US04912101

Reaction notes

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