Phosphorus oxychloride → HCID 59334802, compound

HRID 1942266Notes

Reaction equation

HRID 1942266 reaction equation
[F:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][C:11](O)([C:14]#[N:15])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.P(Cl)(Cl)(Cl)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>N1C=CC=CC=1>[F:1][C:2]1[C:3]([N:8]2[CH2:9][CH:10]=[C:11]([C:14]#[N:15])[CH2:12][CH2:13]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 62657Potassium Phosphate, TribasicHCID 86641933HCID 86641933, compound

Product 1

HCID 59334802HCID 59334802, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

3′-Fluoro-4-hydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonitrile 19 (100 g, 450.2 mMol) was dissolved in dry pyridine (1,000 mL) and cooled to 0° C. under nitrogen. Phosphorus oxychloride (85 mL, 940 mMol) was added dropwise ensuring the temperature did not rise above 10° C. during the addition, and the resulting mixture stirred at 0° C. overnight using a lagged cooling bath. The mixture was cautiously poured into ice-water (3,000 mL) with stirring, and the pH adjusted to 6.0 using potassium phosphate buffer. The mixture was extracted with ethyl acetate (3×2,000 mL), dried (MgSO4) and the solvent evaporated to dryness in vacuo to leave orange oil. Flash chromatography of the residue eluting with hexanes:ethyl acetate (10:1) gave the title compound 20 (65 g, 72%) as a white solid m.p.=76-77° C. δH {400 MHz, CDCl3} 8.01 (1H, d, J=5 Hz), 7.27 (1H, dd, J=20, 8 Hz), 6.79 (1H, m), 6.71 (1H, m), 4.16 (2H, dd, J=12, 3 Hz), 3.65 (2H, t, J=6 Hz), 2.50 (2H, m).

Workup

  1. additiondid not rise above 10° C. during the addition
  2. temperaturea lagged cooling bath
  3. stirringwith stirring
  4. extractionThe mixture was extracted with ethyl acetate (3×2,000 mL)
  5. dry with materialdried (MgSO4)
  6. customthe solvent evaporated to dryness in vacuo
  7. customto leave orange oil
  8. washFlash chromatography of the residue eluting with hexanes:ethyl acetate (10:1)

Sources & evidence

ORD record
ord-5a68df95fff140e3a2a32ce9d0ba65c6
Source dataset
uspto-grants-2013_03
Patent number
US08389549B2

Reaction notes

Loading…