4-Methoxybenzylamine → (4-Methoxy-benzyl)-(3-trifluoromethyl-pyridin-2-yl)-amine

HRID 1801760Notes

Reaction equation

HRID 1801760 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:12][O:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][NH2:19])=[CH:16][CH:15]=1.CCN(C(C)C)C(C)C>C(O)CCC>[CH3:12][O:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][NH:19][C:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 754524-MethoxybenzylamineHCID 81531DiisopropylethylamineHCID 5898332-Chloro-3-(trifluoromethyl)pyridine

Product 1

HCID 29558569(4-Methoxy-benzyl)-(3-trifluoromethyl-pyridin-2-yl)-amineYield 83.1%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-chloro-3-trifluoromethylpyridine (64.83 g, 357 mmol), 4-methoxybenzylamine (56 mL, 429 mmol) and DIPEA (73.4 mL, 429 mmol) in n-butanol (100 mL) was refluxed (oil bath temp. 140° C.) for 3.5 days. Concentrated in vacuum, partitioned between 25% HCl and TBME, reextracted the organic layer twice with 25% HCl, the aqueous layer was made alkaline with 32% NaOH, extracted with TBME, washed with brine and dried over Na2SO4. Removal of the solvent in vacuum left a brown oil (105.21 g, 104%). Vacuum distillation gave the title compound as a colorless liquid (83.766 g, 83%, 4877-2/2; by 139-141° C. at 1.4 mbar). MS (ISP) 283.3 [(M+H)+].

Workup

  1. concentrationConcentrated in vacuum
  2. custompartitioned between 25% HCl and TBME
  3. extractionextracted with TBME
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customRemoval of the solvent in vacuum
  7. waitleft a brown oil (105.21 g, 104%)
  8. distillationVacuum distillation

Sources & evidence

ORD record
ord-246f5eb7827b4d4d83ddba7059ca04d1
Source dataset
uspto-grants-2013_01
Patent number
US08349844B2

Reaction notes

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