1,2-Dimethoxyethane → 2-Amino-4'-bromo-3'-methoxybiphenyl-4-carbonitrile

HRID 389207

Reaction equation

HRID 389207 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[O:9][CH3:10].[F-].[Cs+].Cl.[NH2:14][C:15]1[CH:20]=[C:19]([C:21]#[N:22])[CH:18]=[CH:17][C:16]=1B(O)O.COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CCOC(C)=O>[NH2:14][C:15]1[CH:20]=[C:19]([C:21]#[N:22])[CH:18]=[CH:17][C:16]=1[C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([O:9][CH3:10])[CH:4]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 121872021-Bromo-4-iodo-2-methoxybenzene2×HCID 441187662-Amino-4-cyanobenzeneboronic acid hydrochloride

Product 1

HCID 594088822-Amino-4'-bromo-3'-methoxybiphenyl-4-carbonitrile

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of the product from Step 1, -bromo-4-iodo-2-methoxybenzene (750 mg, 2.4 mmol), CsF (1.09 g, 7.2 mmol), (2-amino-4-cyanophenyl)boronic acid hydrochloride (390 mg, 2.4 mmol), and Pd(PPh3)4 (277 mg, 0.24 mmol) was added DME (15 mL) under nitrogen. It was then heated to 100° C. After 36 hours, EtOAc and water were added to the resulting thick red suspension. The organic layer was washed with brine, dried over Na2SO4, and the solvent was removed in vacuo. The residue was purified on silica (gradient elution, 3-50% EtOAc/hexanes) to yield the title compound as a red oil. LRMS (M+H)+=303.1.

Workup

  1. washThe organic layer was washed with brine
  2. dry with materialdried over Na2SO4
  3. customthe solvent was removed in vacuo
  4. customThe residue was purified on silica (gradient elution, 3-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f67ab53650414a3d9211dda5317f50ee
Source dataset
uspto-grants-2013_02
Patent number
US08377874B2

Linked notes

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