Triethyl phosphite → Diethyl (3-((5-(trifluoromethyl)pyridin-2-yl)oxy)benzyl)phosphonate

HRID 1666318Notes

Reaction equation

HRID 1666318 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:17]=[CH:18][CH:19]=1)[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][N:8]=1.[CH2:20]([O:22][P:23]([O:27]CC)[O:24][CH2:25][CH3:26])[CH3:21]>>[CH2:20]([O:22][P:23]([CH2:2][C:3]1[CH:19]=[CH:18][CH:17]=[C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][N:8]=2)[CH:4]=1)(=[O:27])[O:24][CH2:25][CH3:26])[CH3:21]

Participants

3

Reactant 2

HCID 31215Triethyl phosphite2×HCID 668758802-(3-(Chloromethyl)phenoxy)-5-(trifluoromethyl)pyridine

Product 1

HCID 86623890Diethyl (3-((5-(trifluoromethyl)pyridin-2-yl)oxy)benzyl)phosphonateYield 91%

Conditions

Temperature
150 °C

Procedure

2-(3-Chloromethyl-phenoxy)-5-trifluoromethyl-pyridine (4.88 g, 17.0 mmol) from Step 2 was treated neat with triethylphosphite (4.36 mL, 25.4 mmol) and heated to 150° C. After 6 h, the reaction mixture was cooled, treated with an additional 0.5 mL triethylphosphite (2.9 mmol) and reheated to 150° C. After 6 h, the reaction mixture was removed from the heat and slowly treated with heptane (about 60 mL) while stirring to afford a white solid. The solid was collected by filtration, washed with heptane and dried in a vacuum oven for 16 h at 45° C. to afford a white powder (5.99 g, 91% yield). MS (APCI) M+1=390.1; 1H NMR (400 MHz, CDCl3) δ ppm 1.26 (t, J=7.02 Hz, 6H) 3.18 (d, J=21.83 Hz, 2H) 3.99-4.10 (m, 4H) 7.01 (d, J=8.58 Hz, 1H) 7.03-7.08 (m, 1H) 7.12 (q, J=2.21 Hz, 1H) 7.19-7.24 (m, 1H) 7.38 (t, J=7.90 Hz, 1H) 7.90 (dd, J=8.58, 2.53 Hz, 1H) 8.43 (dd, J=1.66, 0.88 Hz, 1H).

Workup

  1. temperaturethe reaction mixture was cooled
  2. customreheated to 150° C
  3. waitAfter 6 h
  4. customthe reaction mixture was removed from the
  5. temperatureheat
  6. additionslowly treated with heptane (about 60 mL)
  7. customto afford a white solid
  8. filtrationThe solid was collected by filtration
  9. washwashed with heptane
  10. customdried in a vacuum oven for 16 h at 45° C.

Sources & evidence

ORD record
ord-d394d0eb5ce44551a43d2822316c0dfc
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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