1-Hydroxybenzotriazole hydrate → 2-(3-Fluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide

HRID 844053Notes

Reaction equation

HRID 844053 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[O:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=O.[NH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([OH:29])([CH3:28])[CH3:27])=[CH:22][CH:21]=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=N)C>CN(C)C=O.O>[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[O:5][C:6]1[N:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([OH:29])([CH3:27])[CH3:28])=[CH:22][CH:21]=1)=[O:10]

Participants

7

Reactant 4

HCID 27960291-Hydroxybenzotriazole hydrateHCID 101542112-[4-(Aminomethyl)phenyl]propan-2-olHCID 122026432-(3-Fluorophenoxy)nicotinic acidHCID 21883477Ethylcarbodiimide hydrochloride

Product 1

HCID 226123702-(3-Fluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamideYield 98.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution 2-(3-Fluoro-phenoxy)-nicotinic acid (0.250 g, 1.07 mmole), 2-(4-Aminomethyl-phenyl)-propan-2-ol (0.195 grams, 1.18 mmole) and 1-hydroxybenzotriazole hydrate (0.173 grams, 1.28 mmole) in dry dimethylformamide (15 ml) was added 1-(3-dimethylamino)-propyl)-3-ethylcarbodiimide hydrochloride (0.173 grams, 1.28 mmole) and stirred over night. The mixture was diluted with 300 ml water and extracted with ethyl acetate. The combined organics were washed with water and brine, dried over MgSO4, filtered and concentrated to give an oil that was purified by chromatography on silica. Recrystalization from ethyl acetate/hexane gave a solid (0.400 g). M.P. 106-108° C.; Anal. calcd. for C22H21N2O3F: C, 69.46; H, 5.56; N, 7.36. Found: C, 69.05; H, 5.68; N, 7.25.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organics were washed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give an oil that
  7. customwas purified by chromatography on silica
  8. customRecrystalization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-7d5a6692ef39421eaf430d19ffdc3612
Source dataset
uspto-grants-2002_04
Patent number
US06380218B1

Reaction notes

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