Sodium hydride → HCID 69086142, compound

HRID 2362401Notes

Reaction equation

HRID 2362401 reaction equation
[Br-].[Br:2][C:3]1[CH:4]=[N:5][CH:6]=[C:7]([CH2:9]P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:8]=1.[H-].[Na+].[F:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=1[C:39](=O)[CH3:40]>O1CCCC1>[Br:2][C:3]1[CH:4]=[N:5][CH:6]=[C:7](/[CH:9]=[C:39](\[C:33]2[CH:34]=[C:35]([F:38])[CH:36]=[CH:37][C:32]=2[F:31])/[CH3:40])[CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 747941-(2,5-Difluorophenyl)ethan-1-oneHCID 178419456HCID 178419456, compound

Product 1

HCID 69086142HCID 69086142, compoundYield 21.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 3-bromo-5-((tri-phenylphosphino)methyl)pyridine bromide salt (200 mg, 0.337 mmol) in tetrahydrofuran (Volume: 4 mL) was added sodium hydride (90 mg, 0.843 mmol) at 0° C. A half hour later, 2′,5′-difluoroacetophenone (47.0 mL, 0.371 mmol) in tetrahydrofuran (Volume: 1 mL) was added to above solution. Ice bath was removed and heat it to reflux for overnight. Next morning, 10 mL water was added slowly then was extracted by ether (10 mL×3), combined all organic layers, dried over magnesium sulfate, concentrated and obtained a yellow oil which was purified by Preparative HPLC (Preparative HPLC Method 21) and obtained (Z)-3-bromo-5-(2-(2,5-difluorophenyl)prop-1-enyl)pyridine (22 mg, 0.071 mmol, 21.04%). 1H NMR (500 MHz, DMSO-d6) δ 8.45 (d, J=2.1 Hz, 1H), 8.11 (d, J=1.5 Hz, 1H), 7.49 (t, J=2.0 Hz, 1H), 7.36-7.17 (m, 3H), 6.71 (s, 1H), 2.20 (d, J=1.2 Hz, 3H), Mass spec.: 312.1 (MH)+. and (E)-3-bromo-5-(2-(2,5-difluorophenyl)prop-1-enyl)pyridine (18 mg, 0.058 mmol, 17.21%). 1H NMR (500 MHz, DMSO-d6) δ 8.64 (dd, J=6.7, 1.8 Hz, 2H), 8.11 (t, J=1.8 Hz, 1H), 7.38 (ddd, J=9.3, 6.1, 3.2 Hz, 1H), 7.32 (td, J=9.7, 4.7 Hz, 1H), 7.28-7.21 (m, 1H), 6.72 (s, 1H), 2.23 (t, J=1.5 Hz, 3H), Mass spec.: 312.1 (MH)+.

Workup

  1. customIce bath was removed
  2. temperatureheat it
  3. temperatureto reflux for overnight
  4. additionNext morning, 10 mL water was added slowly
  5. extractionthen was extracted by ether (10 mL×3)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customobtained a yellow oil which
  9. customwas purified by Preparative HPLC (Preparative HPLC Method 21)

Sources & evidence

ORD record
ord-723eb51e582d4ebbbbf52613c7dd35a4
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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