4-Amino-1-Boc-piperidine → (S)-tert-butyl 4-(2-(6-bromopyridin-3-yloxy)-4-hydroxybutanamido)piperidine-1-carboxylate

HRID 407945Notes

Reaction equation

HRID 407945 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C[Al](C)C.[Br:19][C:20]1[N:25]=[CH:24][C:23]([O:26][C@H:27]2[CH2:31][CH2:30][O:29][C:28]2=[O:32])=[CH:22][CH:21]=1>C(Cl)Cl.C1(C)C=CC=CC=1>[Br:19][C:20]1[N:25]=[CH:24][C:23]([O:26][C@@H:27]([CH2:31][CH2:30][OH:29])[C:28]([NH:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)=[O:32])=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 12682914-Amino-1-Boc-piperidineHCID 16682925TrimethylaluminumHCID 86688098(S)-3-(6-bromopyridin-3-yloxy)dihydrofuran-2(3H)-one

Product 1

HCID 86688099(S)-tert-butyl 4-(2-(6-bromopyridin-3-yloxy)-4-hydroxybutanamido)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl 4-aminopiperidine-1-carboxylate (0.93 g, 4.65 mmol) in DCM (15 mL) was added dropwise 2M trimethylaluminum (2.8 mL, 5.7 mmol) in toluene. The resulting mixture was stirred for 15 minutes, and (S)-3-(6-bromopyridin-3-yloxy)dihydrofuran-2(3H)-one (1.0 g, 3.87 mmol) in DCM (10 mL) was added slowly over 5 minutes and the reaction stirred at ambient temperature for 2 hours. The reaction was slowly quenched by the addition of 5% tartaric acid (5 mL), saturated NaHCO3 (5 mL) and DCM (10 mL). The organic layer was separated, dried over MgSO4, filtered and concentrated in vacuo to provide (S)-tert-butyl 4-(2-(6-bromopyridin-3-yloxy)-4-hydroxybutanamido)piperidine-1-carboxylate. The crude material was taken on without a further purification.

Workup

  1. stirringthe reaction stirred at ambient temperature for 2 hours
  2. customThe reaction was slowly quenched by the addition of 5% tartaric acid (5 mL), saturated NaHCO3 (5 mL) and DCM (10 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-485708134a8a40eaac525a8478d814e0
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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