1,2-Dimethoxyethane → 3-(2-Methoxy-phenyl)-pyridine-2-carbaldehyde

HRID 250943Notes

Reaction equation

HRID 250943 reaction equation
Br[C:2]1[C:3]([CH:8]=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1B(O)O.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.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>[CH3:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:2]1[C:3]([CH:8]=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 164142313-Bromopyridine-2-carbaldehyde

Product 1

HCID 865947503-(2-Methoxy-phenyl)-pyridine-2-carbaldehydeYield 63.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

A stirred solution of 3-bromo-pyridine-2-carbaldehyde (128 mg, 0.69 mmol) and 2-methoxybenzeneboronic acid (111 mg, 0.73 mmol) in a mixture of THF (0.75 mL), DME (2.0 mL) and 2M Na2CO3 (0.75 mL) was degassed with Ar for 15 minutes, after which Pd(PPh3)4 (41 mg, 0.034 mmol) was added and the heterogeneous mixture heated to 90° C. overnight. The reaction was quenched with brine (15 mL) and diluted with EtOAc (40 mL). The organic layer was separated, washed with brine (4×15 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (EtOAc/Hexanes, 80:20, then 70:30) gave 3-(2-methoxy-phenyl)-pyridine-2-carbaldehyde (93 mg, 63%) as a yellow solid. 1H NMR (CDCl3) δ 3.74 (s, 3H), 6.99 (d, 1H, J=8.3 Hz), 7.10 (t, 1H, J=7.5 Hz), 7.25 (dd, 1H, J=7.4, 1.7 Hz), 7.40-7.49 (m, 1H), 7.55 (dd, 1H, J=7.9, 4.8 Hz), 7.74 (dd, 1H, J=7.9, 1.8 Hz), 8.80 (dd, 1H, J=4.6, 1.5 Hz), 9.95 (s, 1H).

Workup

  1. customwas degassed with Ar for 15 minutes
  2. customThe reaction was quenched with brine (15 mL)
  3. additiondiluted with EtOAc (40 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (4×15 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography on silica gel (EtOAc/Hexanes, 80:20

Sources & evidence

ORD record
ord-85214d310efd41b6949f2476fcfd623b
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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