Potassium Phosphate, Tribasic → 4-cyclopropyl-3-Methoxyaniline

HRID 1465120Notes

Reaction equation

HRID 1465120 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[O:9][CH3:10].[CH:11]1(B(O)O)[CH2:13][CH2:12]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1.O>[CH:11]1([C:2]2[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=2[O:9][CH3:10])[CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 70182544-Bromo-3-methoxyaniline

Product 1

HCID 593949554-cyclopropyl-3-MethoxyanilineYield 25%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22272177Toluene waterSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 4-bromo-3-methoxyaniline (1 g, 4.98 mmol) in 3:2 toluene/water (10 mL) was added cyclopropylboronic acid (514 mg, 5.98 mmol), Pd(OAc)2 (56 mg, 0.25 mmol), PCy3 (140 mg, 0.5 mmol) and K3PO4 (3.18 g, 15 mmol) at room temperature. The mixture was stirred at 100° C. for 10 h. The solid was filtered and the filtrate concentrated in vacuo. Purification by silica gel chromatography (2-10% ethyl acetate/hexanes) provided 4-cyclopropyl-3-methoxyaniline (200 mg, 25%) as a brown solid. 1H NMR (300 MHz, CDCl3) 6.67 (d, J=7.8 Hz, 1H), 6.24-6.20 (m, 2H), 3.82 (s, 3H), 3.50 (brs, 2H), 2.02-1.95 (m, 1H), 0.85-0.79 (m, 2H), 0.57-0.51 (m, 2H).

Workup

  1. filtrationThe solid was filtered
  2. concentrationthe filtrate concentrated in vacuo
  3. customPurification by silica gel chromatography (2-10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-3f0f68352ffb44aab8b111ddf37bddac
Source dataset
uspto-grants-2015_04
Patent number
US08999976B2

Reaction notes

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