Methanol → 1-(3-Chloro-5-fluoro-4-pyridyl)-4-(oxetan-3-yl)piperazine

HRID 524874Notes

Reaction equation

HRID 524874 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:14])[C:7]=1[N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[O:15]1[CH2:18][C:17](=O)[CH2:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>C1COCC1>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:14])[C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH:17]2[CH2:18][O:15][CH2:16]2)[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 887MethanolHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 867209301-(3-Chloro-5-fluoro-4-pyridyl)piperazine

Product 1

HCID 867209311-(3-Chloro-5-fluoro-4-pyridyl)-4-(oxetan-3-yl)piperazine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 1-(3-chloro-5-fluoropyridin-4-yl)piperazine (900 mg, 4.173 mmol) in THF (9.000 mL) was added 3-oxetanone (601.4 mg, 8.346 mmol). To this mixture, under N2, was added sodium triacetoxyborohydride (2.034 g, 9.598 mmol) portionwise over 5 min and the reaction mixture was stirred at RT overnight. MeOH (2 ml) was added to the flask before the mixture was concentrated in vacuo. The residue was partitioned between water (50 ml) and EtAOc (50 ml). The aqueous phase was basified to pH 7-8 with NH4OH. Combined organics washed with brine (30 ml), dried over Na2SO4, filtered and concentrated in vacuo to afford 1-(3-chloro-5-fluoro-4-pyridyl)-4-(oxetan-3-yl)piperazine as a cream solid that was used in next step without further purification. MS (ES+) 272.1.

Workup

  1. concentrationwas concentrated in vacuo
  2. customThe residue was partitioned between water (50 ml) and EtAOc (50 ml)
  3. washCombined organics washed with brine (30 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bc1bd869d1784be087d5eb73250e1384
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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