4-Amino-1-Boc-piperidine → tert-Butyl 4-(1-oxoisoindolin-2-yl)piperidine-1-carboxylate

HRID 1715155Notes

Reaction equation

HRID 1715155 reaction equation
CO[C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10]Br.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CO.C(N(CC)CC)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([N:26]2[CH2:10][C:5]3[C:4](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:3]2=[O:12])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

5

Reactant 2

HCID 12682914-Amino-1-Boc-piperidineHCID 2734813Methyl 2-(bromomethyl)benzoate

Product 1

HCID 11522569tert-Butyl 4-(1-oxoisoindolin-2-yl)piperidine-1-carboxylateYield 54%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 2-bromomethyl-benzoic acid methyl ester (1.50 g, 6.55 mmol, 1.0 equiv; [CAS RN 2417-73-4]) in methanol (12.5 mL) and triethylamine (1.10 mL) was added 4-amino-piperidine-1-carboxylic acid tert-butyl ester (1.38 g, 6.88 mmol, 1.05 equiv; commercially available) and the reaction stirred at rt overnight. The reaction mixture was poured on crashed ice, extracted with ethyl acetate, the combined organic phases washed with water and a sat. solution of NaCl, dried over MgSO4 and concentrated by evaporation under reduced pressure. The crude material was purified with silica column chromatography eluting with hexane/ethyl acetate (1:1) followed by crystallization from hexane/ethyl acetate to obtain 1.12 g (54%) of the title compound as white crystals. MS (ISP): 261.0 [M-tert-Bu+H]+.

Workup

  1. additionThe reaction mixture was poured
  2. extractionextracted with ethyl acetate
  3. washthe combined organic phases washed with water
  4. dry with materiala sat. solution of NaCl, dried over MgSO4
  5. concentrationconcentrated by evaporation under reduced pressure
  6. customThe crude material was purified with silica column chromatography
  7. washeluting with hexane/ethyl acetate (1:1)
  8. customfollowed by crystallization from hexane/ethyl acetate

Sources & evidence

ORD record
ord-6a1b4b67f4454c7b9a3f4d8343d3a073
Source dataset
uspto-grants-2010_09
Patent number
US07799806B2

Reaction notes

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