4-Fluoro-1-naphthoic acid → 4-Fluoro-N-[1-(4-fluorophenyl)-1-hydroxy-3-(2,2,3,3-tetrafluoro-1,4-benzodioxin-6-yl)propan-2-yl]naphthalene-1-carboxamide

HRID 1610623Notes

Reaction equation

HRID 1610623 reaction equation
[NH2:1][CH:2]([CH2:12][C:13]1[CH:26]=[CH:25][C:16]2[O:17][C:18]([F:24])([F:23])[C:19]([F:22])([F:21])[O:20][C:15]=2[CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[F:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]([C:38](O)=[O:39])=[CH:30][CH:29]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]([C:38]([NH:1][CH:2]([CH2:12][C:13]2[CH:26]=[CH:25][C:16]3[O:17][C:18]([F:24])([F:23])[C:19]([F:22])([F:21])[O:20][C:15]=3[CH:14]=2)[CH:3]([C:5]2[CH:6]=[CH:7][C:8]([F:11])=[CH:9][CH:10]=2)[OH:4])=[O:39])=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 684484-Fluoro-1-naphthoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22261655HCID 22261655, compound

Product 1

HCID 222619264-Fluoro-N-[1-(4-fluorophenyl)-1-hydroxy-3-(2,2,3,3-tetrafluoro-1,4-benzodioxin-6-yl)propan-2-yl]naphthalene-1-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of (1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(2,2,3,3-tetrafluoro-2,3-dihydro-1,4-benzodioxin-6-yl)propan-1-ol (250 mg, 0.67 mmol) in acetonitrile (20 ml) were added 4-fluoronaphthalenecarboxylic acid (127 mg, 0.67 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (191 mg, 1.00 mmol) and 1-hydroxybenzotriazole-hydrate (102 mg, 0.67 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). Recrystallization from ethyl acetate-hexane gave the objective substance (290 mg, 80%).

Workup

  1. extractionextracted with ethyl acetate (100 ml×2)
  2. washThe extract was washed successively with water and saturated brine
  3. dry with materialdried (anhydrous magnesium sulfate)
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate)
  6. customRecrystallization from ethyl acetate-hexane
  7. customgave the objective substance (290 mg, 80%)

Sources & evidence

ORD record
ord-bf29fa05b2a64f83be86cd7ba4d0c0ec
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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