Hydrochloric Acid → 3-Hydroxymethyl-2,3'-bipyridyl

HRID 7325Notes

Reaction equation

HRID 7325 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](O)=[O:8])[C:2]=1[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1.C(N(CC)CC)C.[BH4-].[Na+].CO.Cl>O1CCCC1>[OH:8][CH2:7][C:3]1[C:2]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[N:1][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 23423222HCID 23423222, compound

Product 1

HCID 160370823-Hydroxymethyl-2,3'-bipyridylYield 84.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a continually stirred, ice-cold solution of 2,3′-bipyridine-3-carboxylic acid (0.28 g, 1.40 mmole) in dry tetrahydrofuran (10 ml) and triethylamine (0.20 ml, 1.43 mmole) ethyl chloroformate (0.14 ml, 1.46 mmole) was added drop-by-drop over a 30 minute period. The precipitated product was then filtered and washed several times with tetrahyrofuran (3×2 ml). The THF phases were combined, cooled to +10° C., and while stirring under an argon atmosphere, sodium borohydride (0.185 g, 4.9 mmole) was added and then methanol (0.90 ml, 22.2 mmole) was added drop-by-drop over a 1 hour period during which time the temperature increased to 20° C. (Soai et al., 1987). The material was stirred for an additional 1 hour at room temperature. Then, 1N hydrochloric acid was carefully added, the solvent was evaporated under vacuum to 5 ml and washed with dichloromethane (3×5 ml). Sodium carbonate (0.85 g) was added to the aqueous phase, which was then extracted with dichloromethane. The combined fractions were dried with magnesium sulfate and evaporated under vacuum (2 Hg mm, 45° C.) giving a pure product (0.22 g, 84%). 1H-NMR, δ, ppm, 8.71 (1H, dd, J=2.1, 0.6 Hz, C2′-H), 8.55 (1H, dd, J=4.8, 1.5 Hz, C6-H), 8.52 (1H, dd, J=4.8, 1.8 Hz, C6′-H), 7.95 (1H, dd, J=7.8, 1.5 Hz, C4-H), 7.91 (1H, ddd, J=7.8, 2.1, 1.8 Hz, C4′-H), 7.35 (1H, ddd, J=7.8, 4.8, 0.6 Hz, C5′-H), 7.31 (1H, dd, J=7.8, 4.8 Hz, C5-H), 4.58 (2H, s, CH2—O).

Workup

  1. filtrationThe precipitated product was then filtered
  2. washwashed several times with tetrahyrofuran (3×2 ml)
  3. temperaturecooled to +10° C.
  4. stirringwhile stirring under an argon atmosphere
  5. stirringThe material was stirred for an additional 1 hour at room temperature
  6. customthe solvent was evaporated under vacuum to 5 ml
  7. washwashed with dichloromethane (3×5 ml)
  8. additionSodium carbonate (0.85 g) was added to the aqueous phase, which
  9. extractionwas then extracted with dichloromethane
  10. dry with materialThe combined fractions were dried with magnesium sulfate
  11. customevaporated under vacuum (2 Hg mm, 45° C.)

Sources & evidence

ORD record
ord-1c85433b4ec64678bbc860768912d388
Source dataset
uspto-grants-2006_08
Patent number
US07087106B2

Reaction notes

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