Hydrochloric Acid → HCID 66718376, compound

HRID 876969Notes

Reaction equation

HRID 876969 reaction equation
[OH:1][C:2]1([C:8]2[N:13]=[C:12]([C:14]#[N:15])[CH:11]=[CH:10][CH:9]=2)[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.Cl.CO>C1COCC1>[OH:1][C:2]1([C:8]2[N:13]=[C:12]([CH2:14][NH2:15])[CH:11]=[CH:10][CH:9]=2)[CH2:3][CH2:4][O:5][CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 66718480HCID 66718480, compound

Product 1

HCID 66718376HCID 66718376, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

6-(4-Hydroxytetrahydropyran-4-yl)pyridine-2-carbonitrile (ca. 18.9 mmol) was dissolved in anhydrous THF (80 mL) and a 1 M solution of BH3 in THF (95 mL, 95 mmol) added. The solution was stirred at ambient temperature for 2.5 hours, then quenched with methanol. The solution was adjusted to pH 1 by addition of 2 N hydrochloric acid solution and then neutralised to pH 5 with a 5 N solution of sodium hydroxide. Extraction with dichloromethane was followed by addition of further 2 N sodium hydroxide to the aqueous phase until the pH reached 14. This phase was twice extracted with dichloromethane and these combined extracts were evaporated to give a yellow gum. The aqueous extracts were acidified with 2 N hydrochloric acid and concentrated to dryness to yield a white residue. Three trituration of this residue with methanol and concentration of the methanolic liquors yielded a second crop of yellow gum. Drying in vacuo gave the title compound (2.51 g, 64%) as a foamy yellow solid; NMR δH (400 MHz, DMSO) 8.53 (1H, br s), 7.85 (1H, t, J 7.8 Hz), 7.62 (1H, d, J 7.8 Hz), 7.34 (1H, d, J 7.5 Hz), 5.75 (1H, s), 3.72 (4H, m), 3.16 (2H, s), 2.29 (2H, m), 1.42 (1H, d, J 12.3 Hz); LC-MS Retention time 0.43 min, (M+H)+ 209.

Workup

  1. customquenched with methanol
  2. additionThe solution was adjusted to pH 1 by addition of 2 N hydrochloric acid solution
  3. extractionExtraction with dichloromethane
  4. additionwas followed by addition of further 2 N sodium hydroxide to the aqueous phase until the pH
  5. extractionThis phase was twice extracted with dichloromethane
  6. customthese combined extracts were evaporated
  7. customto give a yellow gum
  8. concentrationconcentrated to dryness
  9. customto yield a white residue
  10. customDrying in vacuo

Sources & evidence

ORD record
ord-b0f0221b3724485d83521543f8970f82
Source dataset
uspto-grants-2015_03
Patent number
US08987279B2

Reaction notes

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