1,8-Diazabicyclo(5.4.0)undec-7-ene → 1-(3-Chloropyridin-2-yl)methanamine--hydrogen chloride (1/2)

HRID 1935446Notes

Reaction equation

HRID 1935446 reaction equation
[Cl:1][C:2]1[C:3]([CH2:8]O)=[N:4][CH:5]=[CH:6][CH:7]=1.C1(P([N:24]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C1CCN2C(=NCCC2)CC1>C1(C)C=CC=CC=1>[ClH:1].[ClH:1].[NH2:24][CH2:8][C:3]1[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 10486967(3-Chloropyridin-2-yl)methanol

Product 1

HCID 224645021-(3-Chloropyridin-2-yl)methanamine--hydrogen chloride (1/2)

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a 0° C. solution of 738 mg (5.16 mmol) of 3-chloro-2-(hydroxymethyl)pyridine in 10 mL of toluene, was added 2.13 g (7.74 mmol) of diphenylphosphoryl azide followed by 1.18 g (7.74 mmol) of DBU. After stirring at room temperature overnight, the reaction was partitioned between EtOAc and sat. aq. NaHCO3. The organic layer was separated and the aqueous phase was washed with EtOAc (3×). The combined organic extracts were dried (MgSO4) and concentrated to a dark oil. This resultant crude residue was chromatographed on SiO2 using 10:90 EtOAc-hexanes to afford the title compound contaminated with an aromatic impurity. Triphenylphosphine (1.63 g, 6.20 mmol) was added to a solution of the crude azide in THF:H2O (10:0.5 mL). After stirring overnight, the reaction was concentrated. This residue was diluted with EtOAc, and HCl (2.6M in ]EtOAc) was added dropwise to precipitate out the amine hydrochloride. Stirring was continued for 20 min, after which time the mixture was filtered and rinsed with EtOAc to afford the title compound as a white solid: 1H NMR (CD3OD) δ8.57 (d, 1H, 4.7 Hz), 7.94 (d, 1H, 8.1 Hz), 7.44 (dd, 1H, 4.7, 8.0 Hz), 4.40 (s, 2 Hz).

Workup

  1. customthe reaction was partitioned between EtOAc and sat. aq. NaHCO3
  2. customThe organic layer was separated
  3. washthe aqueous phase was washed with EtOAc (3×)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. concentrationconcentrated to a dark oil
  6. customThis resultant crude residue was chromatographed on SiO2 using 10:90 EtOAc-hexanes

Sources & evidence

ORD record
ord-56318ecdfa414c38ba79fa30b8260b29
Source dataset
uspto-grants-2002_05
Patent number
US06387911B1

Reaction notes

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