Water → 4-(4-Nitro-3-trifluoromethyl-phenylamino)-piperidine-1-carboxylic acid [1-(4-ethoxy-phenyl)-piperidin-4-ylmethyl]-methyl-amide

HRID 511151Notes

Reaction equation

HRID 511151 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[CH3:13][NH:14][CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][C:25](C(F)(F)F)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1.C(N([CH2:37][CH3:38])CC)C.[N+:39]([C:42]1[CH:47]=[CH:46][C:45]([NH:48][CH:49]2[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)=[CH:44][C:43]=1[C:55]([F:58])([F:57])[F:56])([O-:41])=[O:40].[OH2:59]>C(#N)C>[CH2:37]([O:59][C:25]1[CH:24]=[CH:23][C:22]([N:19]2[CH2:18][CH2:17][CH:16]([CH2:15][N:14]([CH3:13])[C:5]([N:52]3[CH2:51][CH2:50][CH:49]([NH:48][C:45]4[CH:46]=[CH:47][C:42]([N+:39]([O-:41])=[O:40])=[C:43]([C:55]([F:58])([F:56])[F:57])[CH:44]=4)[CH2:54][CH2:53]3)=[O:11])[CH2:21][CH2:20]2)=[CH:27][CH:26]=1)[CH3:38]

Participants

7

Reactant 5

HCID 962WaterHCID 8471TriethylamineHCID 94429TriphosgeneHCID 43448257N-(4-Nitro-3-(trifluoromethyl)phenyl)piperidin-4-amineHCID 62648464Methyl-[1-(4-trifluoromethyl-phenyl)-piperidin-4-ylmethyl]-amine

Product 1

HCID 585768574-(4-Nitro-3-trifluoromethyl-phenylamino)-piperidine-1-carboxylic acid [1-(4-ethoxy-phenyl)-piperidin-4-ylmethyl]-methyl-amide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Triphosgene (60 mg; 0.20 mmol) is added to a solution of methyl-[1-(4-trifluoromethyl-phenyl)-piperidin-4-ylmethyl]-amine (150 mg; 0.60 mmol) and triethylamine (185 μL; 1.33 mmol) in acetonitrile (6 mL). After stirring for 15 minutes a solution of (4-nitro-3-trifluoromethyl-phenyl)-piperidin-4-yl-amine (173 mg; 0.60 mmol, in acetonitrile (10 mL) is added. After 2 hours reaction time at room temperature, the mixture is poured into water (10 m) and the aqueous layer is extracted with ethyl acetate (3×50 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography on silica gel (Ethyl acetate:heptane 8:2) to afford the desired product (267 mg; 0.45 mmol). The structure was confirmed using Protocol II-E. Calculated mass=564; observed mass=564; HPLC retention time=7.73 min.

Workup

  1. customAfter 2 hours reaction time at room temperature
  2. extractionthe aqueous layer is extracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product is purified by column chromatography on silica gel (Ethyl acetate:heptane 8:2)

Sources & evidence

ORD record
ord-6e820a468081423999eb4ce5a2f5ffd6
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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