Allylamine → Hydrochloric Acid

HRID 1043769Notes

Reaction equation

HRID 1043769 reaction equation
CC([O-])(C)C.[Na+].[Cl:7][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[CH:10][N:9]=1.[CH2:15]([NH2:18])[CH:16]=[CH2:17]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH2:15]([NH:18][C:8]1[C:13]([F:14])=[CH:12][CH:11]=[CH:10][N:9]=1)[CH:16]=[CH2:17].[ClH:7]

Participants

7

Reactant 3

HCID 7853AllylamineHCID 27827912-Chloro-3-fluoropyridineHCID 23676156Sodium t-butoxide

Product 2

HCID 313Hydrochloric AcidYield 438.8%HCID 592520213-Fluoro-N-2-propen-1-yl-2-pyridinamine

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
67.5 °C

Procedure

To a preformed bright-yellow complex of Pd(dppf)Cl2CH2Cl2 (41 mg, 0.05 mmol), dppf (83 mg, 0.15 mmol) and NaOt-Bu (1.4 g, 15 mmol) in THF (20 mL) was added 2-chloro-3-fluoropyridine (1.32 g, 10 mmol) and allylamine (1.2 mL, 15 mmol). The mixture was sparged with nitrogen and the pressure vessel was capped and sealed. The reaction was heated at 65-70° C. for 16 hours. The cooled reaction was filtered through a plug of Celite and the pad was washed with EtOAc (30 mL). The solvent was removed under reduced pressure to give a brown thick oil. The crude product was purified by silica gel chromatography eluting with 5% MeOH in EtOAc. The product-containing fractions were diluted with EtOAc (100 mL) and extracted with 1 M HCl (2×50 mL). The aqueous acidic product was lyophilized to a light brown solid giving N-allyl-3-fluoropyridin-2-amine as an HCl salt (1.6 g, 85%). LC/MS (m/z): 153.1 (MH+), Rt 0.5 minutes.

Workup

  1. customThe mixture was sparged with nitrogen
  2. customthe pressure vessel was capped
  3. customsealed
  4. customThe cooled reaction
  5. filtrationwas filtered through a plug of Celite
  6. washthe pad was washed with EtOAc (30 mL)
  7. customThe solvent was removed under reduced pressure
  8. customto give a brown thick oil
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 5% MeOH in EtOAc
  11. additionThe product-containing fractions were diluted with EtOAc (100 mL)
  12. extractionextracted with 1 M HCl (2×50 mL)

Sources & evidence

ORD record
ord-a761c9e1ac6c481ea1ce1daa66d2a634
Source dataset
uspto-grants-2013_10
Patent number
US08563549B2

Reaction notes

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