Triethylamine → N-tert-Butyl-3-((4-(2-fluoro-4-nitrobenzoyl)piperazin-1-yl)methyl)benzamide

HRID 1878341Notes

Reaction equation

HRID 1878341 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.[C:33]([NH:37][C:38](=[O:52])[C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][N:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)[CH:40]=1)([CH3:36])([CH3:35])[CH3:34]>C(#N)C>[C:33]([NH:37][C:38](=[O:52])[C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([CH2:45][N:46]2[CH2:47][CH2:48][N:49]([C:4](=[O:6])[C:3]3[CH:7]=[CH:8][C:9]([N+:11]([O-:13])=[O:12])=[CH:10][C:2]=3[F:1])[CH2:50][CH2:51]2)[CH:40]=1)([CH3:36])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 3026792-Fluoro-4-nitrobenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66877987N-tert-butyl-3-(piperazin-1-ylmethyl)benzamide

Product 1

HCID 57917650N-tert-Butyl-3-((4-(2-fluoro-4-nitrobenzoyl)piperazin-1-yl)methyl)benzamideYield 21.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Fluoro-4-nitrobenzoic acid (5 g, 27.01 mmol) was dissolved in acetonitrile (150 mL) and triethylamine (7.53 mL, 54.02 mmol). N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (7.8 g, 40.52 mmol) was added, followed by N-tert-butyl-3(piperazin-1-ylmethyl)benzamide (7.44 g, 27.01 mmol). The reaction was stirred at room temperature for 18 hours and concentrated under vacuum. The residue was dissolved in ethyl acetate, filtered through dicalite, washed consecutively with water (×2) and brine and concentrated under vacuum. The product was purified by strong cation exchange chromatography, eluting macroporous polystyrene sulfonic acid with 2M ammonia in methanol. The resulting solution was concentrated under vacuum to afford the title compound as a pale yellow oil (2.6 g). MS (ESI) m/z 443.7 [M+H]+

Workup

  1. concentrationconcentrated under vacuum
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. filtrationfiltered through dicalite
  4. washwashed consecutively with water (×2) and brine
  5. concentrationconcentrated under vacuum
  6. customThe product was purified by strong cation exchange chromatography
  7. washeluting macroporous polystyrene sulfonic acid with 2M ammonia in methanol
  8. concentrationThe resulting solution was concentrated under vacuum

Sources & evidence

ORD record
ord-559c21fcfaca44f6999aa5ec8515c44c
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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