Hydrochloric Acid → 3-(Pyridin-2-yl)benzaldehyde

HRID 2086474Notes

Reaction equation

HRID 2086474 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.Br[C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH:17]=[O:18].Cl>[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH:17]=[O:18]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 79732-BromopyridineHCID 765833-BromobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 37100393-(Pyridin-2-yl)benzaldehydeYield 38.2%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a THF solution (8 mL) of 2-bromopyridine (1.30 g, 8.23 mmol) at −78° C. was added 1.6 M n-BuLi in hexanes (5.3 mL, 8.48 mmol). The resulting dark red solution was stirred at −78° C. for 10 min, and a solution of 0.5 M ZnCl2 in THF (18 mL, 9.0 mmol) was added giving a light brown slurry. After warming to room temperature, 3-bromobenzaldehyde (0.816 mL, 7.0 mmol) and Pd(PPh3)4 (0.242 g, 0.21 mmol) were added, and the mixture was stirred for 18 h at room temperature under argon. The reaction mixture was poured into 1 N HCl (30 mL) and washed with diethyl ether. The aqueous layer was neutralized with NaHCO3 and extracted with diethyl ether. The solvent was removed in vacuo to give the crude product as an oil. Purification by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane gave 0.49 g (38%) of the desired 3-(2-pyridinyl)benzaldehyde product as a colorless oil. GCMS: m/z=183[+].

Workup

  1. customgiving a light brown slurry
  2. temperatureAfter warming to room temperature
  3. stirringthe mixture was stirred for 18 h at room temperature under argon
  4. washwashed with diethyl ether
  5. extractionextracted with diethyl ether
  6. customThe solvent was removed in vacuo
  7. customto give the crude product as an oil
  8. customPurification by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-7696b171e92643e394d02dd123102d7c
Source dataset
uspto-grants-2004_04
Patent number
US06723753B2

Reaction notes

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