4-Methoxybenzylamine → (6-Chloro-4-trifluoromethyl-pyridin-2-yl)-(4-methoxy-benzyl)-amine

HRID 1481540Notes

Reaction equation

HRID 1481540 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[N:3]=1.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][CH:16]=1>N1C=CC=CC=1>[Cl:12][C:4]1[N:3]=[C:2]([NH:20][CH2:19][C:18]2[CH:21]=[CH:22][C:15]([O:14][CH3:13])=[CH:16][CH:17]=2)[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=1

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 5209682,6-Dichloro-4-(trifluoromethyl)pyridine

Product 1

HCID 86657407(6-Chloro-4-trifluoromethyl-pyridin-2-yl)-(4-methoxy-benzyl)-amine

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 2,6-dichloro-4-trifluoromethyl-pyridine (5.04 g, 23.3 mmol) in pyridine (10 mL) was treated with 4-methoxybenzylamine (9.19 mL, 70.0 mmol) and heated to 110° C. for 26 h. The mixture was cooled, and pyridine (8 mL) was removed in vacuo. The remaining material was diluted with water (50 mL) and extracted twice with EtOAc (75 mL, and 50 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 115-g SEPRA Si 35 SPE column (Flow rate=35 mL/min; Eluent=EtOAc-hexanes, 1:99 for 15 min, then 1:99 to 1:9 over 40 min, 1:9 for 2 min, then 1:9 to 1:4 over 20 min) to yield (6-chloro-4-trifluoromethyl-pyridin-2-yl)-(4-methoxy-benzyl)-amine as a colorless oil, which solidified upon standing. 1H-NMR (400 MHz, CDCl3) δ: 7.26 (d, J=8.6 Hz, 2H), 6.88 (d, J=8.6 Hz, 2H), 6.77 (s, 1H), 6.44 (s, 1H), 5.21 (br. s., 1H), 4.44 (d, J=5.6 Hz, 2H), 3.80 (s, 3H). Mass Spectrum (LCMS, ESI pos.): Calculated for C14H12N2OClF3: 317.1 (M+H). Measured: 317.1.

Workup

  1. temperatureThe mixture was cooled
  2. custompyridine (8 mL) was removed in vacuo
  3. additionThe remaining material was diluted with water (50 mL)
  4. extractionextracted twice with EtOAc (75 mL, and 50 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on a 115-g SEPRA Si 35 SPE column (Flow rate=35 mL/min
  8. wait1:99 to 1:9 over 40 min
  9. wait1:9 for 2 min

Sources & evidence

ORD record
ord-1863797f8bdf4d9e9e545384c3a61d51
Source dataset
uspto-grants-2016_08
Patent number
US09409915B2

Reaction notes

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