Methylamine → N-Methyl-4-anisidine

HRID 2266968Notes

Reaction equation

HRID 2266968 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[CH3:10][NH2:11].CC([O-])(C)C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].CC(O)(C)C>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([NH:11][CH3:10])=[CH:3][CH:4]=1

Participants

6

Reactant 3

HCID 6329MethylamineHCID 121674-ChloroanisoleHCID 23676156Sodium t-butoxide

Product 1

HCID 22250N-Methyl-4-anisidine

Reagents, catalysts & solvents 2

HCID 25112666BrettPhos PalladacycleCatalystHCID 6386tert-ButanolSolvent

Procedure

Following general procedure A, a mixture of 4-chloroanisole (123 μL, 1.0 mmol), 2M methylamine (1 mL, 2.0 mmol), NaOt-Bu (120 mg, 1.2 mmol), BrettPhos precatalyst 10 (8 mg, 0.01 mmol), and t-BuOH (1 mL) was stirred at room temperature for 2 h. The crude product was purified via column chromatography (20:1 CH2Cl2/MeOH) to provide the title compound as a yellow liquid that turned into a tan solid upon standing (126 mg, 92%). 1H NMR (400 MHz, CDCl3) δ: 6.80 (dt, J=9.0, 2.3 Hz, 2H), 6.59 (dt, J=9.0, 2.3 Hz, 2H), 3.76 (s, 3H), 3.46 (bs, 1H), 2.81 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3) δ: 152.2, 143.9, 115.1, 113.8, 56.1, 31.8 ppm. Ali, H. I.; Tomita, K.; Akaho, E.; Kambara, H.; Miura, S.; Hayakawa, H.; Ashida, N.; Kawashima, Y.; Yamagishi, T.; Ikeya, H.; Yoneda, F.; Nagamatsu, T. Bioorg. Med. Chem. 2007, 15, 242.

Workup

  1. customThe crude product was purified via column chromatography (20:1 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-3286cc7fcac240c2a478feac05b494ad
Source dataset
uspto-grants-2010_12
Patent number
US07858784B2

Reaction notes

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