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

HRID 402877Notes

Reaction equation

HRID 402877 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][N:22]=1)[C:17](O)=[O:18].[BH4-].[Na+].Cl>C1COCC1.O>[Cl:13][C:14]1[CH:15]=[C:16]([CH2:17][OH:18])[CH:20]=[CH:21][N:22]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 2369852-Chloroisonicotinic acidHCID 4311764Sodium borohydride

Product 1

HCID 7062237(2-Chloropyridin-4-yl)methanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Carbonyldiimidazole (CDI, 7.88 g, 46.2 mmol, 1.5 equiv) is added at room temperature to a solution of 2-chloroisonicotinic acid (5.0 g, 30.8 mmol) in THF (70 ml). The reaction mixture is stirred at rt overnight, and then added dropwise to a cold (0° C.) solution of NaBH4 (6.07 g, 154 mmol, 5.0 eq) in water (175 ml). After stirring for 10 minutes at 0° C., HCl (2 M aqueous solution) is carefully added. Volatiles are removed via rotary evaporation, and the residue is dissolved in an aqueous 10% solution of NaHCO3. After five extractions with EtOAc, the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. 1H-NMR analysis of the residue indicated adequate purity for direct use of the product (4.40 g, 99%) in the next step. 1H NMR (400 MHz, CDCl3): δ=8.37 (d, J=5.1 Hz, 1H), 7.39 (s, 1H), 7.23 (d, J=5.1 Hz, 1H), 4.78 (s, 2H). MS (ES+): 144 (M+H)+.

Workup

  1. stirringAfter stirring for 10 minutes at 0° C.
  2. customVolatiles are removed via rotary evaporation
  3. dissolutionthe residue is dissolved in an aqueous 10% solution of NaHCO3
  4. extractionAfter five extractions with EtOAc
  5. dry with materialthe combined organic layers are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ba7639d22ac640dc8d1d6062abfe100f
Source dataset
uspto-grants-2014_06
Patent number
US08742132B2

Reaction notes

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