Diisopropylethylamine → 1-(2-Cyclopropyl-acetyl)-piperidine-4-carboxylic acid (4-isopropyl-phenyl)-amide

HRID 2381165Notes

Reaction equation

HRID 2381165 reaction equation
[CH:1]1([CH2:4][C:5]([OH:7])=O)[CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH:44]([C:47]1[CH:52]=[CH:51][C:50]([NH:53][C:54]([CH:56]2[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]2)=[O:55])=[CH:49][CH:48]=1)([CH3:46])[CH3:45]>C(#N)C>[CH:44]([C:47]1[CH:48]=[CH:49][C:50]([NH:53][C:54]([CH:56]2[CH2:61][CH2:60][N:59]([C:5](=[O:7])[CH2:4][CH:1]3[CH2:2][CH2:3]3)[CH2:58][CH2:57]2)=[O:55])=[CH:51][CH:52]=1)([CH3:46])[CH3:45]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 138440Cyclopropaneacetic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 18071890Piperidine-4-carboxylic acid (4-isopropyl-phenyl)-amide

Product 1

HCID 510009101-(2-Cyclopropyl-acetyl)-piperidine-4-carboxylic acid (4-isopropyl-phenyl)-amideYield 96.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Cyclopropylacetic acid (0.055 g) was dissolved in acetonitrile (6 ml), ethyl-diisopropyl-amine (0.129 g), BOP (0.221 g) was added at RT under an argon atmosphere and the mixture was stirred for 30 minutes at RT. Then piperidine-4-carboxylic acid (4-isopropyl-phenyl)-amide (0.123 g) in acetonitrile (2 ml) was added dropwise at RT and the reaction mixture was stirred for 12 h until completion of the reaction. It was then partitioned between ethyl acetate and aqueous 1M HCl, the layers were separated and the aqueous layer washed with 2M aqueous KHCO3 then dried over Na2SO4. The solvent was evaporated off, the residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 60%) to give 1-(2-cyclopropyl-acetyl)-piperidine-4-carboxylic acid (4-isopropyl-phenyl)-amide (0.158 g) as an off-white solid. MS (ESI): 329.17 (MH+).

Workup

  1. stirringthe reaction mixture was stirred for 12 h until completion of the reaction
  2. customIt was then partitioned between ethyl acetate and aqueous 1M HCl
  3. customthe layers were separated
  4. washthe aqueous layer washed with 2M aqueous KHCO3
  5. dry with materialthen dried over Na2SO4
  6. customThe solvent was evaporated off
  7. customthe residue purified by flash chromatography (AcOEt/heptane, gradient from 0 to 60%)

Sources & evidence

ORD record
ord-97e22edef6894f588d24ba980e2972d5
Source dataset
uspto-grants-2012_09
Patent number
US08258158B2

Reaction notes

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