Ammonium Chloride → N-(1-ethyl-3-fluoro-1,2,5,6-tetrahydro-pyridin-4-yl)benzamide

HRID 1257565Notes

Reaction equation

HRID 1257565 reaction equation
[I-].[C:2]([NH:10][C:11]1[CH:16]=[CH:15][N+:14]([CH2:17][CH3:18])=[CH:13][C:12]=1[F:19])(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[BH4-].[Na+].[Cl-].[NH4+].C(=O)(O)[O-].[Na+]>CO>[CH2:17]([N:14]1[CH2:15][CH2:16][C:11]([NH:10][C:2](=[O:9])[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[C:12]([F:19])[CH2:13]1)[CH3:18]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 673241664-Benzamido-1-ethyl-3-fluoro-pyridinium iodide

Product 1

HCID 56954900N-(1-ethyl-3-fluoro-1,2,5,6-tetrahydro-pyridin-4-yl)benzamideYield 78.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 4-benzamido-1-ethyl-3-fluoro-pyridinium iodide (6.45 kg, 17.3 mol) in methanol (40 L) was charged with sodium borohydride (1.82 kg, 43.3 mol) via portion-wise addition over five to six hours maintaining an internal reaction temperature between −5° C. and 10° C. Following this addition saturated aqueous ammonium chloride (10 L) was added and the reaction mixture stirred for 1 h, and then saturated aqueous sodium bicarbonate (12 L) was added and the mixture was left to stand overnight. Methanol was removed under vacuum and the resulting aqueous solution was extracted with ethyl acetate (3×30 L), washed with water, brine and dried over sodium sulfate. The concentrated organic layer yielded 3.36 kg of N-(1-ethyl-3-fluoro-1,2,5,6-tetrahydro-pyridin-4-yl)benzamide (78%). 1H NMR (400 MHz, CDCl3) δ 7.78 (2H, d, J=7.7 Hz), 7.48 (4H, dq, J=14.9, 7.4 Hz), 3.17 (2H, s), 2.89 (2H, s), 2.65 (2H, t, J=5.6 Hz), 2.55 (2H, q, J=7.1 Hz), 1.13 (3H t, J=7.2 Hz).

Workup

  1. temperaturemaintaining an internal reaction temperature between −5° C. and 10° C
  2. additionwas added
  3. waitthe mixture was left
  4. waitto stand overnight
  5. customMethanol was removed under vacuum
  6. extractionthe resulting aqueous solution was extracted with ethyl acetate (3×30 L)
  7. washwashed with water, brine
  8. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-037782df4cf04a41b1e4423337aef243
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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