2-Benzyloxy-6-bromopyridine → 6-(benzyloxy)-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridin-2-amine

HRID 2063376Notes

Reaction equation

HRID 2063376 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:3]=1.[CH3:16][C:17]1([CH3:31])[C:21]([CH3:23])([CH3:22])[O:20][B:19]([C:24]2[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=2)[O:18]1.CC(C)([O-])C.[Na+]>C(O)(C)(C)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>[CH2:9]([O:8][C:4]1[N:3]=[C:2]([NH:28][C:27]2[CH:26]=[CH:25][C:24]([B:19]3[O:20][C:21]([CH3:23])([CH3:22])[C:17]([CH3:31])([CH3:16])[O:18]3)=[CH:30][CH:29]=2)[CH:7]=[CH:6][CH:5]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

7

Reactant 3

HCID 8174752-Benzyloxy-6-bromopyridineHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 23676156Sodium t-butoxide

Product 1

HCID 582225306-(benzyloxy)-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyridin-2-amineYield 65%

Reagents, catalysts & solvents 3

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylCatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 2-bromo-6-benzyloxypyridine (1.10 g, 4.15 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.00 g, 4.57 mmol, 1.1 eq.) in tert-butyl alcohol (20 mL) was added sodium tert-butoxide (556 mg, 5.78 mmol, 1.40 eq.), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (98 mg, 0.25 mmol, 0.06 eq.), and bis(dibenzylideneacetone)palladium(0) (96 mg, 0.17 mmol, 0.04 eq.). The reaction mixture was purged with nitrogen for a few minutes, and the dark orange reaction mixture was heated under microwave irradiation (300 watts, 120° C.) for 15 minutes. The reaction was quenched with 10% aqueous citric acid and poured into ethyl acetate. The organic layer was washed with water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in heptane) to give the desired product (l-1) (1.08 g, 65% yield) as slightly brown solid. 1H NMR (CDCl3, 400 MHz) δ ppm 7.75 (d, J=8.4 Hz, 2H), 7.49 to 7.41 (m, 3H), 7.41 to 7.34 (m, 4H), 7.34 to 7.27 (m, 1H), 6.46 (s, 1H), 6.44 (d, J=7.9 Hz, 1H), 6.30 (d, J=7.9 Hz, 1H), 5.37 (s, 2H), 1.34 (s, 12H).

Workup

  1. customThe reaction mixture was purged with nitrogen for a few minutes
  2. customThe reaction was quenched with 10% aqueous citric acid
  3. additionpoured into ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-a76c027e01324f579a5578a08d63d9b4
Source dataset
uspto-grants-2012_10
Patent number
US08288381B2

Reaction notes

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