Acetic Acid → 1-[4-(2-Chloro-3-fluoro-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone

HRID 1355531Notes

Reaction equation

HRID 1355531 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2].[Cl:10][C:11]1[C:16]([F:17])=[C:15]([CH:18]=O)[CH:14]=[CH:13][N:12]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>ClCCCl>[Cl:10][C:11]1[C:16]([F:17])=[C:15]([CH2:18][N:7]2[CH2:8][CH2:9][N:4]([C:1](=[O:3])[CH3:2])[CH2:5][CH2:6]2)[CH:14]=[CH:13][N:12]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 837951-AcetylpiperazineHCID 27631602-Chloro-3-fluoro-4-formylpyridineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 185069231-[4-(2-Chloro-3-fluoro-pyridin-4-ylmethyl)-piperazin-1-yl]-ethanone

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-Acetylpiperazine (0.164 g, 1.28 mmol) was dissolved in 5 mL DCE and the resulting solution was added to 2-chloro-3-fluoro-pyridine-4-carbaldehyde (14-2, 0.170 g, 1.07 mmol). NaBH(OAc)3 (0.248 g, 1.17 mmol) was added followed by the addition of 0.100 mL of HOAc. After 45 min the reaction was quenched with sat NaHCOC3 (aq). The mixture was extracted 3× with DCM, and the organic extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (10 g column, DCM (for 4 min) gradient to 95:5 DCM/MeOH (over 8 min)), desired comes off shortly after 95:5 is attained (13 min) affording good separation from close peak preceeding desired. Afforded pure titled compound. 1H NMR (CDCl3) δ 8.18 (d, 1H, J=4.9 Hz), 7.38 (t, 1H, J=4.6 Hz), 3.66 (m, 4H), 3.50-3.48 (m, 2H), 2.50-2.46 (m, 4H), 2.09 (s, 3H).

Workup

  1. customAfter 45 min the reaction was quenched with sat NaHCOC3 (aq)
  2. extractionThe mixture was extracted 3× with DCM
  3. dry with materialthe organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography (10 g column, DCM (for 4 min) gradient to 95:5 DCM/MeOH (over 8 min))
  7. custom(13 min)
  8. customaffording good
  9. customseparation
  10. customfrom close peak

Sources & evidence

ORD record
ord-74355ecd5fcf4af19ae56d9a5c5f3e75
Source dataset
uspto-grants-2003_07
Patent number
US06586424B2

Reaction notes

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