2,2,3,3,3-Pentafluoropropylamine → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(2,2,3,3,3-pentafluoro-propyl)-nicotinamide

HRID 1514686Notes

Reaction equation

HRID 1514686 reaction equation
C[Al](C)C.[F:5][C:6]([F:13])([C:9]([F:12])([F:11])[F:10])[CH2:7][NH2:8].C[O:15][C:16](=O)[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]2[C:26]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)=[N:27][O:28][C:29]=2[CH2:30][OH:31])=[N:19][CH:18]=1>O1CCOCC1>[F:38][C:35]1[CH:36]=[CH:37][C:32]([C:26]2[C:25]([CH2:24][O:23][C:20]3[CH:21]=[CH:22][C:17]([C:16]([NH:8][CH2:7][C:6]([F:13])([F:5])[C:9]([F:12])([F:11])[F:10])=[O:15])=[CH:18][N:19]=3)=[C:29]([CH2:30][OH:31])[O:28][N:27]=2)=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 790022,2,3,3,3-PentafluoropropylamineHCID 16682925TrimethylaluminumHCID 667181316-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 469286666-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(2,2,3,3,3-pentafluoro-propyl)-nicotinamideYield 77.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Trimethylaluminium solution (2 M in toluene, 0.84 mL, 1.67 mmol) was added to a solution of 2,2,3,3,3-pentafluoropropylamine (121 μL, 1.12 mmol) in dioxane (4 mL). After stirring for 45 min at 50° C. a solution of 6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (100 mg, 0.28 mmol) in dioxane (4 mL) was added and stirring was continued overnight at 85° C. The dioxane was removed by distillation. The remaining material was purified by chromatography (silica, ethyl acetate:heptane 1:1) to yield the title compound (103 mg, 77%) as a white solid. MS: m/e=474.2 [M−H]−.

Workup

  1. additionwas added
  2. customThe dioxane was removed by distillation
  3. customThe remaining material was purified by chromatography (silica, ethyl acetate:heptane 1:1)

Sources & evidence

ORD record
ord-cbf25302a47e4408908fc07a5b6c503c
Source dataset
uspto-grants-2012_07
Patent number
US08222246B2

Reaction notes

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