4-Amino-1-Boc-piperidine → (S)-tert-butyl 4-(2-(4-bromo-2-fluoro-5-methylphenoxy)-4-hydroxybutanamido)piperidine-1-carboxylate

HRID 407983Notes

Reaction equation

HRID 407983 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[C:32]([CH3:33])=[CH:31][C:23]([O:24][C@H:25]2[CH2:29][CH2:28][O:27][C:26]2=[O:30])=[C:22]([F:34])[CH:21]=1>C(Cl)Cl>[Br:19][C:20]1[C:32]([CH3:33])=[CH:31][C:23]([O:24][C@@H:25]([CH2:29][CH2:28][OH:27])[C:26]([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:30])=[C:22]([F:34])[CH:21]=1

Participants

5

Reactant 3

HCID 12682914-Amino-1-Boc-piperidineHCID 16682925TrimethylaluminumHCID 67469850(S)-3-(4-bromo-2-fluoro-5-methylphenoxy)dihydrofuran-2(3H)-one

Product 1

HCID 86688114(S)-tert-butyl 4-(2-(4-bromo-2-fluoro-5-methylphenoxy)-4-hydroxybutanamido)piperidine-1-carboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of tert-butyl 4-aminopiperidine-1-carboxylate (2.4 g, 12 mmol) in CH2Cl2 (30 mL) was added trimethylaluminum (6.0 mL, 12 mmol) dropwise. The resulting mixture was stirred for 15 minutes, then (S)-3-(4-bromo-2-fluoro-5-methylphenoxy)dihydrofuran-2(3H)-one (2.9 g, 10 mmol) in CH2Cl2 (30 mL) was added slowly and stirred at ambient temperature for 1 hour. The reaction was slowly quenched with 5% tartaric acid, neutralized with aqueous NaHCO3 and filtered through celite. The filtrate was extracted with CH2Cl2, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford (S)-tert-butyl 4-(2-(4-bromo-2-fluoro-5-methylphenoxy)-4-hydroxybutanamido)piperidine-1-carboxylate (3.2 g, 6.5 mmol, 65% yield).

Workup

  1. stirringstirred at ambient temperature for 1 hour
  2. customThe reaction was slowly quenched with 5% tartaric acid
  3. filtrationfiltered through celite
  4. extractionThe filtrate was extracted with CH2Cl2
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified over silica gel (100% EtOAc)

Sources & evidence

ORD record
ord-24c53e931c6248ebb5f70d7f9942d146
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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