Hydrochloric Acid → alpha-2-Pyridylpyridine-2-methanol

HRID 1167067Notes

Reaction equation

HRID 1167067 reaction equation
[Li]CCCC.[N:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1Br.[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH:19]=[O:20].Cl>CCOCC.O.C1COCC1>[N:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH:19]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][N:13]=1)[OH:20]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 79732-BromopyridineHCID 142732-PyridinecarboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 118763alpha-2-Pyridylpyridine-2-methanolYield 52.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 80 mL n-BuLi in hexanes (2.5 M, 0.2 mol) was added 2-pyridylbromide (31.6 gram 0.2 mol) in 100 mL of ether at −80° C.-−60° C. The suspension was stirred for 1 h, and the temperature was allowed to rise to −45° C. Subsequently 2-pyridinecarboxaldehyde (21.42 gram 0.2 mol) in of ether (100 mL) was added during 30 min. To the thick slurry was added additional THF (200 mL) and the mixture was stirred for 1.5 h at −40° C.-−30° C. and then the mixture was allowed to warm up to −10° C. The mixture was poured into water (200 ml) and acidified with 2 M HCl to pH=1-2 and the layers were separated. The aqueous layer was extracted twice with ether (100 mL) and neutralized with saturated Na2CO3(aq) to pH=8. The aqueous layer was extracted CH2Cl2 (3×100 ml). Drying (Na2SO4) and evaporation of the solvent yielded a brown oil. Vacuum distillation (118° C., 0.2 mmHg) afforded di(2-pyridinyl)methanol (19.42 gram, 104.4 mmol, 52%) as a yellow oil. 1H-NMR (200 MHz. CDCl3) δ 5.88 (s, 2H), 7.11-7.19 (m, 2H), 7.47-7.67 (m, 4H). 8.50-8.54 (m, 2H). 13C-NMR (50.3 MHz, CDCl3) δ 75.0 (d), 121.0 (d), 122.5 (d), 136.8 (d), 1448.1 (d), 160.7 (s).

Workup

  1. customto rise to −45° C
  2. stirringthe mixture was stirred for 1.5 h at −40° C.-−30° C.
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted twice with ether (100 mL)
  5. extractionThe aqueous layer was extracted CH2Cl2 (3×100 ml)
  6. customDrying
  7. custom(Na2SO4) and evaporation of the solvent
  8. customyielded a brown oil
  9. distillationVacuum distillation (118° C., 0.2 mmHg)

Sources & evidence

ORD record
ord-3e4bc65fb227465e8eb10735ce7446ce
Source dataset
uspto-grants-2003_09
Patent number
US06617299B1

Reaction notes

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