Diisopropylethylamine → Tert-butyl 4-[[benzyl-[2-oxo-2-(2-pyridyl)ethyl]amino]methyl]-4-hydroxy-piperidine-1-carboxylate

HRID 72885

Reaction equation

HRID 72885 reaction equation
[CH2:1]([NH:8][CH2:9][C:10]1([OH:23])[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Br.Br[CH2:35][C:36]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=1)=[O:37]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([N:8]([CH2:9][C:10]1([OH:23])[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:12][CH2:11]1)[CH2:35][C:36](=[O:37])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27762312-Bromo-1-(2-pyridinyl)-1-ethanone hydrobromideHCID 68291338Tert-butyl 4-((benzylamino)methyl)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 68291423Tert-butyl 4-[[benzyl-[2-oxo-2-(2-pyridyl)ethyl]amino]methyl]-4-hydroxy-piperidine-1-carboxylateYield 92%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To tert-butyl 4-[(benzylamino)methyl]-4-hydroxy-piperidine-1-carboxylate (3.0 g, 9.36 mmol) in DMF (19 mL) at 0° C. was added diisopropyl ethylamine (3.4 mL, 19.66 mmol) followed by the addition of 2-bromo-1-(2-pyridyl)ethanone hydrobromide salt (2.6 g, 9.36 mmol) and reaction mixture was stirred for 2 hours warming from 0° C. to 10° C. The reaction mixture was diluted with ethyl acetate and washed with sat. NaHCO3 solution and then brine. The organics were separated, dried over Na2SO4, filtered and concentrated in vacuo to give a residue, which was purified using silica gel column chromatography using MeOH/DCM (1-15%) as eluent to give tert-butyl 4-[[benzyl-[2-oxo-2-(2-pyridyl)ethyl]amino]methyl]-4-hydroxy-piperidine-1-carboxylate (3.8, 92%). ESI-MS m/z calc. 439.2. Found 440.0 (M+1)+; Retention time: 1.12 minutes (3 min run).

Workup

  1. temperaturewarming from 0° C. to 10° C
  2. washwashed with sat. NaHCO3 solution
  3. customThe organics were separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a residue, which
  8. customwas purified

Sources & evidence

ORD record
ord-95922c8713b64476bfe983225eb4b428
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Linked notes

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