Sodium hydride → HCID 57459620, compound

HRID 1428503Notes

Reaction equation

HRID 1428503 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([CH2:14][OH:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:19]1[C:24]([Br:25])=[CH:23][CH:22]=[CH:21][N:20]=1>C1COCC1.O>[CH2:1]([N:8]1[CH2:9][CH:10]=[C:11]([CH2:14][O:15][C:19]2[C:24]([Br:25])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH2:12][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydride2×HCID 6933243-Bromo-2-chloropyridineHCID 11264156(1-Benzyl-1,2,3,6-tetrahydropyridin-4-yl)methanol2×

Product 1

HCID 57459620HCID 57459620, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-methanol (0.675 g, 3.019 mmol) [C.A.S. 158984-76-0] in dry THF (40 ml) cooled at 0° C., was added NaH (0.138 g, 3.622 mmol; 60% mineral oil). The resulting reaction mixture was stirred at 0° C. for 30 min. Then, a solution of 2-chloro-3-bromopyridine (0.58 g, 3.019 mmol) in dry THF (10 ml) was added and the mixture was heated in a sealed tube at 85° C. for 2 h. After cooling, additional (1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-methanol (0.675 g, 3.019 mmol), NaH (0.138 g, 3.622 mmol; 60% mineral oil) were added to the reaction mixture, which was then heated at 85° C. overnight. Then, after cooling, the mixture was diluted with water and extracted with EtOAc. The organic phase was separated, dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 2% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate D58 (0.55 g, 50%).

Workup

  1. customThe resulting reaction mixture
  2. temperaturethe mixture was heated in a sealed tube at 85° C. for 2 h
  3. temperatureAfter cooling
  4. temperaturewas then heated at 85° C. overnight
  5. temperatureThen, after cooling
  6. extractionextracted with EtOAc
  7. customThe organic phase was separated
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 2% as eluent)
  11. customThe desired fractions were collected
  12. concentrationconcentrated in vacuo
  13. customto yield intermediate D58 (0.55 g, 50%)

Sources & evidence

ORD record
ord-e49781f3997e40609868c496917608b8
Source dataset
uspto-grants-2015_01
Patent number
US08937060B2

Reaction notes

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