Phosphorus oxychloride → HCID 68352494, compound

HRID 541228Notes

Reaction equation

HRID 541228 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2(O)[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[N:7][CH:8]=1)#[N:2].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=2)=[N:7][CH:8]=1)#[N:2]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 68288835HCID 68288835, compound2×

Product 1

HCID 68352494HCID 68352494, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a stirred mixture of tert-butyl 4-(5-cyanopyridin-2-yl)-4-hydroxypiperidine-1-carboxylate (compound 26.2, 500 mg, 1.65 mmol, 1.00 equiv) in pyridine (20 mL) was added dropwise phosphoryl trichloride (2.5 g, 16.34 mmol, 9.90 equiv) at 10-15° C. The resulting solution was stirred for 18 h at 15˜20° C. The reaction was then carefully quenched by the addition of 20 mL of water and extracted with 3×100 mL of ethyl acetate. The combined organic phases were washed with 2×50 mL of aqueous HCl (1 M) followed by 1×100 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:100 to 1:7) as eluent to yield 0.3 g (64%) of the title compound as a yellow solid.

Workup

  1. customThe reaction was then carefully quenched by the addition of 20 mL of water
  2. extractionextracted with 3×100 mL of ethyl acetate
  3. washThe combined organic phases were washed with 2×50 mL of aqueous HCl (1 M)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified

Sources & evidence

ORD record
ord-765dd088c8fb4299a03d59cf12e5350d
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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