Diethyl 2-Fluorobenzylphosphonate → (E)-2-Bromo-5-fluoro-4-(2-fluorostyryl)pyridine

HRID 2362417Notes

Reaction equation

HRID 2362417 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:7]([F:10])=[CH:8][N:9]=1)[CH:5]=O.[F:11][C:12]1[CH:26]=[CH:25][CH:24]=[CH:23][C:13]=1[CH2:14]P(=O)(OCC)OCC.CC(C)([O-])C.[K+]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4](/[CH:5]=[CH:14]/[C:13]2[CH:23]=[CH:24][CH:25]=[CH:26][C:12]=2[F:11])[C:7]([F:10])=[CH:8][N:9]=1

Participants

5

Reactant 3

HCID 11207329Diethyl 2-FluorobenzylphosphonateHCID 23665647Potassium tert-butoxideHCID 454803282-Bromo-5-fluoroisonicotinaldehyde

Product 1

HCID 86673439(E)-2-Bromo-5-fluoro-4-(2-fluorostyryl)pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-bromo-5-fluoroisonicotinaldehyde (2 g, 9.80 mmol) and diethyl 2-fluorobenzylphosphonate (2.66 g, 10.78 mmol) in tetrahydrofuran (80 mL) at 0° C., was added potassium tert-butoxide(1M in tetrahydrofuran, 12.75 mL, 12.75 mmol) dropwise over a couple of minutes. When addition was complete, the reaction was allowed to stir at 0° C. for 45 min and quenched by addition of saturated ammonium chloride. The reaction was diluted with ether, washed with water (4×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (8%→15% EtOAc/Hex) gave 450 mg as an oil with solid crystallizing from the mixture. The material was triturated with hexanes (2×) to give a fine white powder. 1H NMR (CDCl3) δ: 8.26 (d, J=1.5 Hz, 1H), 7.69 (d, J=5.5 Hz, 1H), 7.64 (td, J=7.6, 1.5 Hz, 1H), 7.54 (d, J=16.8 Hz, 1H), 7.30-7.41 (m, 1H), 7.17-7.26 (m, 2H), 7.11-7.17 (m, 1H). 13C NMR (CDCl3) δ: 161.0, 156.7, 138.8, 136.6, 135.5, 131.0, 129.3, 127.9, 124.6, 123.7, 119.4, 116.3. 19F NMR (CDCl3) δ: −116.72 (br. s., 1F), −136.08 (br. s., 1F).

Workup

  1. additionWhen addition
  2. customquenched by addition of saturated ammonium chloride
  3. additionThe reaction was diluted with ether
  4. washwashed with water (4×)
  5. dry with materialbrine, dried over magnesium sulfate
  6. concentrationconcentrated
  7. customColumn chromatography (8%→15% EtOAc/Hex) gave 450 mg as an oil with solid
  8. customcrystallizing from the mixture
  9. customThe material was triturated with hexanes (2×)
  10. customto give a fine white powder

Sources & evidence

ORD record
ord-1b60d5d35699444ba7a72c25feac6327
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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