Binap, (A+-)- → tert-Butyl 2-(6-bromopyridin-3-ylamino)-5-methylbenzoate

HRID 42003Notes

Reaction equation

HRID 42003 reaction equation
[NH2:1][C:2]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[Br:16][C:17]1[CH:22]=[CH:21][C:20](I)=[CH:19][N:18]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O>[Br:16][C:17]1[N:18]=[CH:19][C:20]([NH:1][C:2]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][C:3]=2[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])=[CH:21][CH:22]=1

Participants

9

Reactant 4

HCID 634876Binap, (A+-)-HCID 47382712-Bromo-5-iodopyridineHCID 13399998tert-Butyl 2-amino-5-methylbenzoateHCID 23676156Sodium t-butoxide

Product 1

HCID 86657255tert-Butyl 2-(6-bromopyridin-3-ylamino)-5-methylbenzoateYield 40.2%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

In a schlenck tube, a mixture of tert-butyl 2-amino-5-methylbenzoate (2.89 mmol, 0.600 g), 2-bromo-5-iodopyridine (2.89 mmol, 0.822 g), BINAP (0.29 mmol, 0.096 g), Pd2(dba)3 (0.14 mmol, 0.132 g) and NaOtBu (5.79 mmol, 0.556 g) in toluene (15 ml) was heated at 120° C. for 3 hours. Water and ethyl acetate were added to the reaction crude. The aqueous phase was extracted again with more ethyl acetate. The organic phase was washed with water and brine, dried, filtered and concentrated in vacuo. The crude mixture was purified by chromatography (Biotage 40S, SiO2, Hexane:Ethyl acetate from 0% to 10%) affording 0.422 g (yield 40%) of the expected product.

Workup

  1. extractionThe aqueous phase was extracted again with more ethyl acetate
  2. washThe organic phase was washed with water and brine
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified by chromatography (Biotage 40S, SiO2, Hexane:Ethyl acetate from 0% to 10%)

Sources & evidence

ORD record
ord-526c59565f6c4553ab53563a4218665a
Source dataset
uspto-grants-2013_09
Patent number
US08536165B2

Reaction notes

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