Isobutyryl chloride → N-[4-Chloro-3-(tetrahydro-pyran-2-yloxymethyl)-pyridin-2-ylmethyl]-isobutyramide

HRID 1959601Notes

Reaction equation

HRID 1959601 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:9])[C:3]=1[CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.[BH4-].[Na+].C([O-])(O)=O.[Na+].[C:25](Cl)(=[O:29])[CH:26]([CH3:28])[CH3:27]>CO.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][NH:9][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])[C:3]=1[CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1

Participants

7

Reactant 4

HCID 62325Isobutyryl chlorideHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 670775644-Chloro-3-(tetrahydro-pyran-2-yloxymethyl)-pyridine-2-carbonitrile

Product 1

HCID 67077984N-[4-Chloro-3-(tetrahydro-pyran-2-yloxymethyl)-pyridin-2-ylmethyl]-isobutyramide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Chloro-3-(tetrahydro-pyran-2-yloxymethyl)-pyridine-2-carbonitrile (30 mg. 0.12 mmol) was dissolved in a mixture of MeOH (0.75 mL) and THF (1 mL). CoCl2 hexahydrate (56 mg. 0.24 mmol) and NaBH4 (45 mg. 1.19 mmol dissolved in 1 mL MeOH) were added. After stirring for 8 min at RT sat. NaHCO3 solution (1 mL) and isobutyryl chloride (125 μL. 1.19 mmol) were added. The solvents were removed in vacuo and the residue was partioned between sat. NH4Cl solution (10 mL) and DCM (10 mL) and extracted with DCM (3×10 ml). The combined organic layers were washed with brine and dried over Na2SO4 filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with hexane/EtOAc 2:1→1:2) to give the title compound. MS (m/z): 326.8 [M+H+]

Workup

  1. additionwere added
  2. customThe solvents were removed in vacuo
  3. extractionextracted with DCM (3×10 ml)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (elution with hexane/EtOAc 2:1→1:2)

Sources & evidence

ORD record
ord-41648101f2f04dd4a93203654b1691ec
Source dataset
uspto-grants-2013_04
Patent number
US08410134B2

Reaction notes

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