Dimethylformamide → HCID 22473215, compound

HRID 2183501Notes

Reaction equation

HRID 2183501 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:17][CH2:16][CH2:15][N:14]2[CH3:18])=[CH:9][N:8]=1.CN([CH:22]=[O:23])C.[BH4-].[Na+].[NH4+].[Cl-]>C1COCC1.CO>[CH3:18][N:14]1[CH2:15][CH2:16][CH2:17][CH:13]1[C:10]1[CH:11]=[CH:12][C:7]([CH2:22][OH:23])=[N:8][CH:9]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 10466854HCID 10466854, compoundHCID 178418339Butyllithium

Product 1

HCID 22473215HCID 22473215, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of BuLi (3.0 mmol) in hexanes (1.6 M, 1.87 ml) was added to a stirred solution of 2-bromo-5-(1-methylpyrrolidin-2-yl)pyridine (480 mg, 2.0 mmol) in THF (50 ml) at −78° C. under N2. The reaction was stirred at −78° C. for 10 min, DMF (462 μl, 6.0 mmol) was added and the reaction allowed to warm slowly to room temperature and stirred at room temperature for a further 1 h. MeOH (50 ml) was added, followed by sodium borohydride (75 mg, 2.0 mmol) and then the reaction mixture was stirred at room temperature for 1 h. NH4Cl solution (10 ml) was added cautiously. The resulting mixture was concentrated under reduced pressure, then dissolved in MeOH/CH2Cl2 (1:1, 50 ml) and dry loaded onto silica. The crude residue was purified by column chromatography on silica using 5% MeOH/CH2Cl2 containing 1% NH3 to yield the desired hydroxymethylpyridine (100 mg, 26%). 1H NMR (400 MHz, CDCl3) δ 8.46 (1H, d, J=2.0 Hz), 7.70 (1H, dd, J=8.0, 2.0 Hz), 7.25 (1H, d, J=8.0 Hz), 4.75 (2H, s), 4.18 (1H, broad s), 3.28-3.18 (1H, m), 3.09 (1H, J=8.3 Hz), 2.31 (1H, q, J=9.0 Hz), 2.22-2.16 (1H, m), 2.16 (3H, s), 2.05-1.65 (3H, m). m/z (ES+) 193 (M+H+).

Workup

  1. temperatureto warm slowly to room temperature
  2. stirringstirred at room temperature for a further 1 h
  3. stirringthe reaction mixture was stirred at room temperature for 1 h
  4. concentrationThe resulting mixture was concentrated under reduced pressure
  5. dissolutiondissolved in MeOH/CH2Cl2 (1:1, 50 ml)
  6. customdry
  7. customThe crude residue was purified by column chromatography on silica using 5% MeOH/CH2Cl2 containing 1% NH3

Sources & evidence

ORD record
ord-75ec24c602b044338e13e20153d3e7d4
Source dataset
uspto-grants-2005_05
Patent number
US06900209B2

Reaction notes

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