Water → 6-(Methylamino)-2-pyridylethanol

HRID 1369202Notes

Reaction equation

HRID 1369202 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].C(O[C:10](=O)[CH2:11][C:12]1[N:17]=[C:16]([NH:18][CH3:19])[CH:15]=[CH:14][CH:13]=1)C.[OH2:21].[OH-].[Na+]>C1COCC1>[CH3:19][NH:18][C:16]1[N:17]=[C:12]([CH:11]([OH:21])[CH3:10])[CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 22507068Ethyl 2-(6-(methylamino)pyridin-2-yl)acetate

Product 1

HCID 223194656-(Methylamino)-2-pyridylethanolYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1.0 M LiAlH4 in THF (95 mL, 95 mmole) was added dropwise to a mechanically stirred suspension of ethyl-2-(methylamino)-6-pyridylacetate (7.34 g, 31.82 mmole) in dry THF (64 mL) at 0° C. under argon. The addition was done slowly until gas evolution subsided, then the remaining solution was added rapidly. Addition required 5-7 min. The reaction was warmed to RT and stirred for 45 min, then was heated to reflux. After 10 min, the reaction was cooled to 0° C. and worked up by sequential dropwise addition of H2O (3.6 mL), 15% NaOH (3.6 mL), and H2O (10.8 mL). The mixture was stirred for 15 min at 0° C. and 15 min at RT, then was filtered through a Buchner funnel. The filter pad was washed with plenty of THF, and the filtrate was concentrated. The residue was reconcentrated from toluene, then was chromatographed on silica gel (5% MeOH in 1:1 EtOAc/CHCl3) to afford the title compound (3.23 g, 67%) as a yellow oil which solidified to a waxy solid: 1H NMR (250 MHz, CDCl3) δ7.36 (dd, J=8.3, 7.3 Hz, 1 H), 6.42 (d, J=7.3 Hz, 1 H), 6.26 (d, J=8.3 Hz, 1 H), 4.93-5.28 (m, 1 H), 4.38-4.60 (m, 1 H), 3.96 (t, J=5.4 Hz, 2 H), 2.90 (d, J=5.2 Hz, 3 H), 2.84 (t, J=5.4 Hz, 2 H); MS (ES) m/e 153 (M+H)+.

Workup

  1. additionThe addition
  2. additionthe remaining solution was added rapidly
  3. additionAddition required 5-7 min
  4. temperaturewas heated to reflux
  5. waitAfter 10 min
  6. temperaturethe reaction was cooled to 0° C.
  7. stirringThe mixture was stirred for 15 min at 0° C. and 15 min at RT
  8. filtrationwas filtered through a Buchner funnel
  9. washThe filter pad was washed with plenty of THF
  10. concentrationthe filtrate was concentrated
  11. customwas chromatographed on silica gel (5% MeOH in 1:1 EtOAc/CHCl3)

Sources & evidence

ORD record
ord-e50765346bb645f3bddfb8d575963e67
Source dataset
uspto-grants-2003_06
Patent number
US06576643B2

Reaction notes

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