Ethyl 4-amino-6-chloronicotinate → (4-Amino-6-chloropyridin-3-yl)methanol

HRID 715089Notes

Reaction equation

HRID 715089 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[NH2:7][C:8]1[C:13]([C:14](OCC)=[O:15])=[CH:12][N:11]=[C:10]([Cl:19])[CH:9]=1>C1COCC1>[NH2:7][C:8]1[CH:9]=[C:10]([Cl:19])[N:11]=[CH:12][C:13]=1[CH2:14][OH:15]

Participants

4

Reactant 2

HCID 824642Ethyl 4-amino-6-chloronicotinateHCID 21226445Aluminium lithium hydride

Product 1

HCID 21073390(4-Amino-6-chloropyridin-3-yl)methanolYield 84.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Treat a 0° C. suspension of lithium aluminum hydride (5.7 g, 150 mmol) in THF (150 mL), under N2, drop-wise with a solution of ethyl 4-amino-6-chloronicotinate (15 g, 75 mmol) in THF (50 mL), allow to warm to RT and stir for 3 h. Quench the mixture with 10% NaOH (5.7 mL), then water (5.7 mL), filter to remove solids, add water to the filtrate and extract with EtOAc (3×). Wash the combined organics with brine, dry and concentrate to give the title compound (10 g, 84%). 1H NMR (300 MHz, DMSO-d6): δ 7.79 (s, 1H), 6.53 (s, 1H), 6.17 (s, 2H), 5.10 (t, J=5.4 Hz, 1H), 4.36 (d, J=5.4 Hz, 2H).

Workup

  1. additionTreat a 0° C.
  2. customQuench the mixture with 10% NaOH (5.7 mL)
  3. filtrationwater (5.7 mL), filter
  4. customto remove solids
  5. additionadd water to the filtrate
  6. extractionextract with EtOAc (3×)
  7. washWash the combined organics with brine
  8. customdry
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-08ef457fe8a249bf951de211617cd37a
Source dataset
uspto-grants-2015_11
Patent number
US09187474B2

Reaction notes

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