Acetic Acid → 2-Chloro-4-(pyrrolidin-1-ylmethyl)pyridine

HRID 1046410

Reaction equation

HRID 1046410 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]=O)[CH:5]=[CH:4][N:3]=1.[NH:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 27629942-Chloro-4-pyridinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 581138712-Chloro-4-(pyrrolidin-1-ylmethyl)pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The mixture of 2-chloro-pyridine-4-carbaldehyde and (300 mg, 2.12 mmol) and pyrrolidine (0.19 mL, 2.12 mmol) in DCM (10 mL) was treated with acetic acid (0.25 mL, 4.24 mmol). The mixture was stirred at room temperature for 10 minutes and NaBH(OAc)3 (899 mg, 4.24 mmol) was added. After overnight stirring, the reaction was washed with sat. NaHCO3 and extracted twice with DCM. The organic layers were combined and washed with water, brine, dried over sodium sulfate, filtrated and concentrated. The crude material was purified by column chromatography with MeOH/DCM (0-10%) and concentrated to give 120 mg of 2-chloro-4-pyrrolidin-1-ylmethyl-pyridine as a clear oil.

Workup

  1. stirringAfter overnight stirring
  2. washthe reaction was washed with sat. NaHCO3
  3. extractionextracted twice with DCM
  4. washwashed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltrated
  7. concentrationconcentrated
  8. customThe crude material was purified by column chromatography with MeOH/DCM (0-10%)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-00b3354c1d864bf2b188acb816f155e2
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Linked notes

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