Methanol → 3-chloro-5-fluoro-4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]pyridine

HRID 524957Notes

Reaction equation

HRID 524957 reaction equation
N[C:2]1[C:13]([C:14]([O:16]N2C3C=CC=CC=3N=N2)=O)=C2N=CC(CC#N)=CN2N=1.[Cl:26][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([F:39])[C:32]=1[C:33]1[CH2:34][CH2:35][NH:36][CH2:37][CH:38]=1.O1CC(=O)C1.CO>C1COCC1>[Cl:26][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([F:39])[C:32]=1[C:33]1[CH2:34][CH2:35][N:36]([CH:13]2[CH2:14][O:16][CH2:2]2)[CH2:37][CH:38]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 150242543-OxetanoneHCID 867210123-Chloro-5-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)pyridineHCID 901998921H-benzo[d][1,2,3]triazol-1-yl 2-amino-6-(cyanomethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

Product 1

HCID 867210133-chloro-5-fluoro-4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]pyridineYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium triacetoxyborohydride (Sodium Ion (1)) (1.026 g, 4.842 mmol) was added in portions to a stirred solution of 3-chloro-5-fluoro-4-(1,2,3,6-tetrahydropyridin-4-yl)pyridine (468 mg, 2.201 mmol) and 3-oxetanone (269.7 mg, 239.9 μL, 3.742 mmol) in THF (10 mL) at 0° C. under an atmosphere of nitrogen. The reaction was allowed to warm to ambient temperature over 16 hours. MeOH (2 mL) was added dropwise and the mixture stirred at ambient temperature for 30 minutes. The mixture was concentrated in vacuo and partitioned between water and EtAOc. The pH of the aqueous layer was adjusted to pH 7-8 by the addition of NH4OH and the layers separated. The aqueous layer was extracted with EtOAc (×3) and the combined organic extracts washed with brine (×1), dried (MgSO4), filtered and concentrated in vacuo to give 3′-chloro-5′-fluoro-1-(oxetan-3-yl)-1,2,3,6-tetrahydro-4,4′-bipyridine as a white solid (573 mg, 97% Yield). MS (ES+) 269.1.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. custompartitioned between water and EtAOc
  3. additionThe pH of the aqueous layer was adjusted to pH 7-8 by the addition of NH4OH
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with EtOAc (×3)
  6. washthe combined organic extracts washed with brine (×1)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-03d12ec3c3b1459dae94568c943345be
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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