Trimethyl orthoformate → 2-Bromo-5-chloro-4-(dimethoxymethyl)pyridine

HRID 1629744Notes

Reaction equation

HRID 1629744 reaction equation
[Br:1][C:2]1[N:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:3]=1C=O.[CH3:11][O:12][CH:13](OC)[O:14][CH3:15].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:6]([CH:13]([O:14][CH3:15])[O:12][CH3:11])[C:7]([Cl:10])=[CH:8][N:9]=1

Participants

6

Reactant 3

HCID 9005Trimethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 575173392-Bromo-5-chloropyridine-3-carbaldehyde

Product 1

HCID 575173382-Bromo-5-chloro-4-(dimethoxymethyl)pyridine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-bromo-5-chloronicotinaldehyde (3.00 g, 13.6 mmol), trimethylorthoformate (4.48 mL, 40.8 mmol) and p-toluenesulfonic acid monohydrate (129 mg, 0.680 mmol) in MeOH (55 mL) was refluxed for 16 hours. The mixture was diluted in CH2Cl2 and washed with 10% aqueous potassium carbonate and brine, dried over sodium sulfate, filtered and concentrated. The crude product was used in the next step without further purification. LC/MS method 2: MS (ESI): 267 [M+H]+, rt=2.22 min. 1H-NMR (DMSO-d6): δ (ppm) 8.53 (s, 1H), 7.65 (S, 1H), 5.53 (s, 1H), 3.31 (2d, 6H).

Workup

  1. temperaturewas refluxed for 16 hours
  2. washwashed with 10% aqueous potassium carbonate and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was used in the next step without further purification
  7. custom267 [M+H]+, rt=2.22 min

Sources & evidence

ORD record
ord-78baa8099b4c4e3f8fee0a0381d60c1b
Source dataset
uspto-grants-2014_07
Patent number
US08791100B2

Reaction notes

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