Phosphate → HCID 66687043, compound

HRID 1025944Notes

Reaction equation

HRID 1025944 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:12][N:11]=[C:10]([CH2:20][OH:21])[CH:9]=2)=[CH:4][CH:3]=1.P([O-])([O-])([O-])=[O:23]>C(#N)C.O.[O-]Cl.[Na+]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:13]([O:14][CH2:15][C:16]([F:17])([F:18])[F:19])=[CH:12][N:11]=[C:10]([C:20]([OH:23])=[O:21])[CH:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 1061PhosphateHCID 66687561[4-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-methanol

Product 1

HCID 66687043HCID 66687043, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 23665760Sodium HypochloriteSolvent

Conditions

Temperature
35 °C

Procedure

[4-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridin-2-yl]-methanol (17.4 g, 55 mmol) was dissolved in acetonitrile (235 mL). Phosphate buffer (pH 6.7, 220 mL) and 2,2,6,6-tetra-methylpiperidine 1-oxyl radical (TEMPO, 0.6 g) was added and the solution was warmed to 35° C. To this warm solution under argon was added with stirring over 2 h simultaneously a solution of NaOCl2 (12.4 g) in water (58 mL) and NaOCl (0.85 mL, 10% solution) in water (35 mL). Stirring was continued for 20 h at 35° C. after which time the solution was cooled to room temperature and quenched by addition of in sequence water (420 mL), 2 N NaOH solution (65 mL) and Na2SO3 solution (17.1 g in 285 mL water). This mixture was stirred for 30 min and acidified with 2 N HCl (175 mL). The mixture was extracted once with ethyl acetate/THF (800/150 mL), and once with ethyl acetate (500 mL). Organic phases were washed with brine (800 mL), pooled and dried with Na2SO4. The solvent phase was concentrated to a volume of ˜100 mL, n-heptane (150 mL) was added and the solvent phase was concentrated again to ˜100 mL. This was repeated twice. n-Heptane (100 mL) was added. The product precipitated upon stirring, was filtered off and dried to give the title compound as a white solid (18.4 g, quant.), LC-MS (UV peak area/ESI) ˜100%, 332.029 (M+H)+.

Workup

  1. additionTo this warm solution under argon was added
  2. temperatureafter which time the solution was cooled to room temperature
  3. customquenched by addition of in sequence water (420 mL), 2 N NaOH solution (65 mL) and Na2SO3 solution (17.1 g in 285 mL water)
  4. stirringThis mixture was stirred for 30 min
  5. extractionThe mixture was extracted once with ethyl acetate/THF (800/150 mL)
  6. washOrganic phases were washed with brine (800 mL)
  7. dry with materialdried with Na2SO4
  8. concentrationThe solvent phase was concentrated to a volume of ˜100 mL, n-heptane (150 mL)
  9. additionwas added
  10. concentrationthe solvent phase was concentrated again to ˜100 mL
  11. additionn-Heptane (100 mL) was added
  12. customThe product precipitated
  13. stirringupon stirring
  14. filtrationwas filtered off
  15. customdried

Sources & evidence

ORD record
ord-14f9180e965441849c471091ee2dc99d
Source dataset
uspto-grants-2014_05
Patent number
US08729105B2

Reaction notes

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