Water → (S)-benzyl 3-(tert-butoxycarbonyl(ethyl)amino)piperidine-1-carboxylate

HRID 919579Notes

Reaction equation

HRID 919579 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:27](Br)[CH3:28].O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH2:27][CH3:28])[C@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6332Ethyl BromideHCID 24758Sodium hydrideHCID 50999241(S)-1-Cbz-3-Boc-Aminopiperidine

Product 1

HCID 68070545(S)-benzyl 3-(tert-butoxycarbonyl(ethyl)amino)piperidine-1-carboxylateYield 55.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-benzyl 3-(tert-butoxycarbonylamino)piperidine-1-carboxylate (500 mg, 1.49 mmol) in DMF (5 mL) was added NaH (60% suspension in mineral oil, 120 mg, 1.64 mmol) and the reaction mixture was stirred for 1 h. To the reaction mixture was added ethyl bromide (0.12 mL, 1.64 mmol) and the reaction mixture was stirred for 4 h. The reaction mixture was diluted with ice-cooled water and the solution was extracted with EtOAc, the EtOAc layer was dried over Na2SO4 and concentrated in vacuo to give the crude product that was purified by column chromatography (silica gel, gradient, EtOAc in hexanes) to give (300 mg, 55%) of the titled compound. 1H NMR (400 MHz, CDCl3): δ 7.36-7.30 (m, 5H), 5.18-5.12 (m, 2H), 4.18-4.13 (m, 2H), 3.68-3.62 (m, 1H), 3.22-3.17 (m, 2H), 3.01-2.85 (m, 1H), 2.68-2.59 (m, 1H), 1.89-1.81 (m, 1H), 1.78-1.73 (m, 2H), 1.55 (s, 9H), 1.54-1.48 (m, 1H), 1.08 (t, J=6.4 Hz, 3H). ES-MS: m/z [M+1]=363.

Workup

  1. stirringthe reaction mixture was stirred for 4 h
  2. additionThe reaction mixture was diluted with ice-
  3. extractionthe solution was extracted with EtOAc
  4. dry with materialthe EtOAc layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give the crude product that
  7. customwas purified by column chromatography (silica gel, gradient, EtOAc in hexanes)

Sources & evidence

ORD record
ord-39b3cf7c121b4431ac0bab30f976f8fe
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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