Dichloromethane → Methyl 2-amino-5-bromo-3-methylbenzoate

HRID 1678246Notes

Reaction equation

HRID 1678246 reaction equation
CB1OB(C)OB(C)O1.[NH2:10][C:11]1[C:20](I)=[CH:19][C:18]([Br:22])=[CH:17][C:12]=1[C:13]([O:15][CH3:16])=[O:14].Cl[CH2:24]Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:10][C:11]1[C:20]([CH3:24])=[CH:19][C:18]([Br:22])=[CH:17][C:12]=1[C:13]([O:15][CH3:16])=[O:14]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 574072Trimethylboroxine2×HCID 53435544Methyl 2-amino-5-bromo-3-iodobenzoate

Product 1

HCID 2763413Methyl 2-amino-5-bromo-3-methylbenzoateYield 1,179.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

2,4,6-Trimethyl-cyclotriboroxane (6.99 ml, 50.0 mmol) was added to a stirred suspension of methyl 2-amino-5-bromo-3-iodo-benzoate (Preparation #11a, 15.5 g, 43.6 mmol), [1,1′-bis(diphenylphosphino)-ferrocene)dichloropalladium(II) 1:1 complexed with dichloromethane (1.67 g, 2.05 mmol) and cesium carbonate (42.9 g, 132 mmol) in 1,4-dioxane (200 mL) under N2. After about 4 hours at about 90° C. additional 2,4,6-trimethyl-cyclotriboroxane (1.00 ml, 7.15 mmol) was added and the reaction was continued with heating for about 2 more hours. The reaction was cooled, filtered through a short pad of silica gel and concentrated to afford an oil. The crude product was purified by flash chromatography over silica gel using heptane:EtOAc (92:8) as the eluent to yield methyl 2-amino-5-bromo-3-methyl-benzoate (5.9 g, 55%) as a pale yellow solid; RP HPLC (Table 1, Method e) Rt=2.72, m/z: (MH)+ 244/246.

Workup

  1. temperaturewith heating for about 2 more hours
  2. temperatureThe reaction was cooled
  3. filtrationfiltered through a short pad of silica gel
  4. concentrationconcentrated
  5. customto afford an oil
  6. customThe crude product was purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-3abdcf13c0814d648d39b67da2587cb3
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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