Hydrochloric Acid → {6-[(5-Fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]pyridin-3-yl}-methanol

HRID 509959Notes

Reaction equation

HRID 509959 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]2[C:13]([O:19][CH3:20])=[N:14][CH:15]=[C:16]([F:18])[CH:17]=2)=[N:6][CH:5]=1.[AlH4-].[Li+].[OH-].[Na+].Cl>O1CCCC1>[F:18][C:16]1[CH:17]=[C:12]([CH2:11][NH:10][C:7]2[N:6]=[CH:5][C:4]([CH2:3][OH:2])=[CH:9][CH:8]=2)[C:13]([O:19][CH3:20])=[N:14][CH:15]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 28112Lithium aluminum hydrideHCID 582593336-[(5-Fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-nicotinic acid methyl ester

Product 1

HCID 58259120{6-[(5-Fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]pyridin-3-yl}-methanolYield 47.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 6-[(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-nicotinic acid methyl ester (91, 0.825 g, 2.83 mmol) in 11 mL of tetrahydrofuran, lithium tetrahydroaluminate (5.66 mL, 1.0 M in tetrahydrofuran, 5.66 mmol) was added at −40° C. under nitrogen. The reaction was allowed to warm to room temperature and stirred overnight. The reaction was poured into aqueous 1M sodium hydroxide, then neutralized with aqueous 1M hydrochloric acid. The solids were filtered out through celite, the celite washed with ethyl acetate and tetrahydrofuran. The isolated aqueous layer was extracted with ethyl acetate and all organic layers were combined, washed with brine, then dried over sodium sulfate, filtered and the filtrate was concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (92, 357 mg). MS (ESI) [M+H+]+=264.4.

Workup

  1. filtrationThe solids were filtered out through celite
  2. washthe celite washed with ethyl acetate and tetrahydrofuran
  3. extractionThe isolated aqueous layer was extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under vacuum
  8. customThe resulting material was purified by silica gel column chromatography
  9. washeluting with ethyl acetate and hexane
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-567d9f4a0eee44dea1aa995ece29f341
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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