Triethylamine → 4-(2-Fluoro-benzyl)-1-[3-(4-fluoro-phenyl)-propionyl]-piperidine-4-carboxylic acid [2-(4-ethyl-phenyl)-ethyl]-amide

HRID 730201Notes

Reaction equation

HRID 730201 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH2:28]([C:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][NH:38][C:39]([C:41]2([CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[F:54])[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)=[O:40])=[CH:32][CH:31]=1)[CH3:29].[F:55][C:56]1[CH:61]=[CH:60][C:59]([CH2:62][CH2:63][C:64](O)=[O:65])=[CH:58][CH:57]=1.C(N(CC)CC)C>O1CCCC1.C(OCC)C>[CH2:28]([C:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][NH:38][C:39]([C:41]2([CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[F:54])[CH2:42][CH2:43][N:44]([C:64](=[O:65])[CH2:63][CH2:62][C:59]3[CH:60]=[CH:61][C:56]([F:55])=[CH:57][CH:58]=3)[CH2:45][CH2:46]2)=[O:40])=[CH:32][CH:31]=1)[CH3:29]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 1363023-(4-Fluorophenyl)propionic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 236009334-(2-Fluoro-benzyl)-piperidine-4-carboxylic acid [2-(4-ethyl-phenyl)-ethyl]-amide

Product 1

HCID 236009324-(2-Fluoro-benzyl)-1-[3-(4-fluoro-phenyl)-propionyl]-piperidine-4-carboxylic acid [2-(4-ethyl-phenyl)-ethyl]-amideYield 40.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.266 g, 0.602 mmol) was added to a solution of 4-(2-fluoro-benzyl)-piperidine-4-carboxylic acid [2-(4-ethyl-phenyl)-ethyl]-amide (0.185 g, 0.502 mmol), 3-(4-fluoro-phenyl)-propionic acid (0.101 g, 0.602 mmol) and triethylamine (0.210 mL, 1.51 mmol) in tetrahydrofuran (5 mL). After 1 h the mixture was diluted with ethyl ether (20 mL), washed with saturated aqueous sodium bicarbonate (20 mL) followed by water (2×10 mL). The organic layer was collected, concentrated under reduced pressure and the crude product purified by column chromatography to give 0.105 g (40 %) of 4-(2-fluoro-benzyl)-1-[3-(4-fluoro-phenyl)-propionyl]-piperidine-4-carboxylic acid [2-(4-ethyl-phenyl)-ethyl]-amide LRMS m/z 519.2 (M+H)+.

Workup

  1. washwashed with saturated aqueous sodium bicarbonate (20 mL)
  2. customThe organic layer was collected
  3. concentrationconcentrated under reduced pressure
  4. customthe crude product purified by column chromatography

Sources & evidence

ORD record
ord-288feefb00534232b9ebfdc1e9690cee
Source dataset
uspto-grants-2009_09
Patent number
US07582654B2

Reaction notes

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