4-Fluorobenzaldehyde → HCID 86303956, compound

HRID 578832Notes

Reaction equation

HRID 578832 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[Li]CCCC.[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=1>C1COCC1>[Cl:16][C:12]1[CH:11]=[C:10]([C:4]2[CH:3]=[C:2]([CH:27]([C:26]3[CH:29]=[CH:30][C:23]([F:22])=[CH:24][CH:25]=3)[OH:28])[CH:7]=[N:6][C:5]=2[O:8][CH3:9])[CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 680234-FluorobenzaldehydeHCID 90415047HCID 90415047, compound2×HCID 178418339Butyllithium

Product 1

HCID 86303956HCID 86303956, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cooled solution, −78° C., of 5-bromo-3-(3-chlorophenyl)-2-methoxypyridine (Intermediate 7, 1.5 g, 5 mmol) in THF (25 mL), under nitrogen, was added nBuLi (4.8 mL, 5.5 mmol) drop-wise over 2 minutes. The reaction mixture was stirred at −78° C. for 40 min. A solution of 4-fluorobenzaldehyde (744 mg, 6 mmol) in THF (2 mL) was added, and the reaction mixture was stirred an additional 30 min at −78° C. The reaction was quenched with saturated sodium sulfate, filtered, and concentrated under reduced pressure. Purification (FCC, SiO2, 0-25% EtOAc/hexanes) afforded the title compound as a colorless solid (1.65 g, 96%). 1H NMR (400 MHz, CD3OD) δ 8.11 (d, J=2.3 Hz, 1H), 7.63 (d, J=2.0 Hz, 1H), 7.51 (s, 1H), 7.47-7.29 (m, 5H), 7.07 (t, J=8.6 Hz, 2H), 5.84 (s, 1H), 3.93 (s, 3H). [M+H]=344.18.

Workup

  1. stirringthe reaction mixture was stirred an additional 30 min at −78° C
  2. customThe reaction was quenched with saturated sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification (FCC, SiO2, 0-25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-608c7c7a0bfd4b2c977862cf0362bb36
Source dataset
uspto-grants-2015_05
Patent number
US09040692B2

Reaction notes

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