3-Tert-butyl-2-methoxy-5-(2-methoxy-3-pyridyl)benzaldehyde → (3-Amino-phenyl)-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-methanol

HRID 2390798Notes

Reaction equation

HRID 2390798 reaction equation
[C:1]([C:5]1[C:6]([O:21][CH3:22])=[C:7]([CH:10]=[C:11]([C:13]2[C:14]([O:19][CH3:20])=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:12]=1)[CH:8]=[O:9])([CH3:4])([CH3:3])[CH3:2].C[Si]([N:27]([Si](C)(C)C)[C:28]1[CH:29]=[C:30]([Mg]Cl)[CH:31]=[CH:32][CH:33]=1)(C)C>C1COCC1>[NH2:27][C:28]1[CH:33]=[C:32]([CH:8]([C:7]2[CH:10]=[C:11]([C:13]3[C:14]([O:19][CH3:20])=[N:15][CH:16]=[CH:17][CH:18]=3)[CH:12]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[C:6]=2[O:21][CH3:22])[OH:9])[CH:31]=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 591567613-Tert-butyl-2-methoxy-5-(2-methoxy-3-pyridyl)benzaldehydeHCID 178504299HCID 178504299, compound

Product 1

HCID 67070064(3-Amino-phenyl)-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-methanolYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

step 1—To a solution of 3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-benzaldehyde (B-2a, R4=tert-Bu, R6═H, 110 mg, 0.368 mmol) in THF (5 mL) at 0° C. was added a solution of 3-(bis-(trimethylsilyl)amino)phenyl magnesium chloride (1.0 M in THF, 0.750 mL, 0.750 mmol). The reaction was gradually warmed RT and stirred overnight. The reaction mixture was quenched with 1N aqueous HCl solution and extracted with EtOAc. The organic layer was washed sequentially with water and brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (25 to 50% EtOAc) to afford 79 mg (55%) of (3-amino-phenyl)-[3-tert-butyl-2-methoxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-methanol (34) as a colorless oil.

Workup

  1. customwas gradually warmed RT
  2. customThe reaction mixture was quenched with 1N aqueous HCl solution
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed sequentially with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by SiO2 chromatography
  9. washeluting with an EtOAc/hexane gradient (25 to 50% EtOAc)

Sources & evidence

ORD record
ord-cdc421ab35c5485892c938faab684fe4
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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