Ethanol → 3-(2-Fluoroethoxy)-4-(4-methylpyridin-3-yl)aniline

HRID 1405072Notes

Reaction equation

HRID 1405072 reaction equation
[F:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([N+:11]([O-])=O)[CH:8]=[CH:7][C:6]=1[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1[CH3:20].[Cl-].[NH4+].CCO>[Zn].C1COCC1>[F:1][CH2:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([CH:8]=[CH:7][C:6]=1[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1[CH3:20])[NH2:11]

Participants

6

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 867200623-(2-(2-Fluoroethoxy)-4-nitrophenyl)-4-methylpyridine

Product 1

HCID 867200633-(2-Fluoroethoxy)-4-(4-methylpyridin-3-yl)anilineYield 97.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Intermediate 16C (254 mg, 0.919 mmol), Zinc (361 mg, 5.52 mmol), and ammonium chloride (344 mg, 6.44 mmol) were taken in a flask followed by addition of EtOH (2 mL) and THF (2 mL). The reaction mixture was stirred at room temperature for 2 hours and filtered through a pad of CELITE®. The filtrate was concentrated to give Intermediate 16 (220 mg, 0.893 mmol, 97% yield) as a yellow solid. MS (ES): m/z=247.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.13 (s, 3 H) 4.07 (dd, J=7.40, 3.39 Hz, 1 H) 4.13-4.20 (m, 1 H) 4.53 (dd, J=4.64, 3.14 Hz, 1 H) 4.65 (dd, J=4.77, 3.26 Hz, 1 H) 5.29 (s, 2 H) 6.28 (dd, J=8.03, 2.01 Hz, 1 H) 6.33 (d, J=2.01 Hz, 1 H) 6.81 (d, J=8.03 Hz, 1 H) 7.23 (d, J=5.02 Hz, 1 H) 8.22 (s, 1 H) 8.32 (d, J=4.77 Hz, 1 H). Intermediate 16 was used in the synthesis of Example 22.

Workup

  1. filtrationfiltered through a pad of CELITE®
  2. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-60ee1bc3b3cd4e86bcf7402a0fd3dc91
Source dataset
uspto-grants-2014_12
Patent number
US08916553B2

Reaction notes

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