Oxygen → 3-((Pyridin-2-yl)amino)propan-1-ol

HRID 658285Notes

Reaction equation

HRID 658285 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:8][CH2:9][CH2:10][CH2:11][OH:12].O=O>O>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:8][CH2:9][CH2:10][CH2:11][OH:12]

Participants

5

Reactant 3

HCID 977OxygenHCID 79772-ChloropyridineHCID 90863-Amino-1-propanol

Product 1

HCID 114124793-((Pyridin-2-yl)amino)propan-1-ol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

Charge 2-chloropyridine (1.0 equiv) and 3-aminopropan-1-ol (2.2 equiv, 1.5 volumes, 1.5 wt equiv) and mix thoroughly. Purge oxygen from the system by applying vacuum (ca −10 psi) to the system and backfilling with nitrogen three times. Heat the solution to 150° C. and hold for 13-16 h under a nitrogen atmosphere. The light yellow to yellow reaction mixture is then cooled to 18-23° C. and water (1.0 volume, 1.0 wt equiv) is added. Extract the mixture three times with i-PrOAc (3×5.0 volumes, 3×4.4 wt equiv). Combine the organic extracts and wash with water (0.5 volumes, 0.5 wt equiv). Concentrate the i-PrOAc solution in vacuo to minimum stir. Tert-butyl methyl ether (5.0 volumes, 3.7 wt equiv) is used to dissolve the residual oil. Add seed crystals (0.1 wt %) of the pure product and hold at 18-23 for 5 h. Cool the mixture to 0-5° C. and hold for 1-2 h. Isolate the crystalline product by filtration and wash twice with tent-butyl methyl ether (2×2 volumes, 2×1.5 wt equiv) at 5-10° C. Dry 3-(2-pyridinylamino)-1-propanol at 25-30° C. under reduced pressure. Percent yield range observed: 60-70%.

Workup

  1. additionmix thoroughly
  2. temperatureThe light yellow to yellow reaction mixture is then cooled to 18-23° C.
  3. extractionExtract the mixture three times with i-PrOAc (3×5.0 volumes, 3×4.4 wt equiv)
  4. washCombine the organic extracts and wash with water (0.5 volumes, 0.5 wt equiv)
  5. concentrationConcentrate the i-PrOAc solution in vacuo to minimum stir
  6. dissolutionto dissolve the residual oil
  7. additionAdd seed crystals (0.1 wt %) of the pure product
  8. waithold at 18-23 for 5 h
  9. temperatureCool the mixture to 0-5° C.
  10. waithold for 1-2 h
  11. customIsolate the crystalline product
  12. filtrationby filtration
  13. washwash twice with tent-butyl methyl ether (2×2 volumes, 2×1.5 wt equiv) at 5-10° C
  14. customat 25-30° C.

Sources & evidence

ORD record
ord-f5fecbc64d5f4e938f8af128ea83cd6c
Source dataset
uspto-grants-2011_12
Patent number
US08076475B2

Reaction notes

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