Piperidine → 3-Amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid

HRID 1867753Notes

Reaction equation

HRID 1867753 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH:17]C(OCC2C3C=CC=CC=3C3C2=CC=CC=3)=O)([C:14]([OH:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC)(C)(C)C.C(O)(C)C.N1CCCCC1>CN(C)C=O>[NH2:17][C:10]1([C:14]([OH:16])=[O:15])[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 27344081-((tert-butoxy)carbonyl)-3-(((9H-fluoren-9-ylmethoxy)carbonyl)amino)piperidine-3-carboxylic acid2×HCID 86616950TBME isopropanol

Product 1

HCID 247296423-Amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acidYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(tert-butoxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}piperidine-3-carboxylic acid was resolved by chiral HPLC resolution {Merck 50 mm 16 μm Kromasil Chirose 2 No. CT9014, tert-butylmethylether/iso-propanol (90/10). The first eluted enantiomer (800 mg, 1.71 mmol) 1-(tert-butoxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}piperidine-3-carboxylic acid (Isomer 1) was dissolved in N,N-dimethylformamide (10 ml) and piperidine (0.85 ml, 8.55 mmol) added. The mixture was stirred at room temperature over night. The resulting white precipitate was filtered off. The filtrates were concentrated and the residues purified by column chromatography on silica eluting with saturated ammonia in methanol/dichloromethane (25/75). The fractions containing the desired product were combined with the filtered solids and evaporated to give 3-amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (Isomer 1) (339 mg, 81%); 1H NMR Spectrum: (D2O) 1.44 (s, 9H); 1.63 (m, 1H); 1.79 (d, 1H); 1.97 (d, 1H); 2.10 (m, 1H); 2.88 (t, 1H); 3.33 (d, 1H); 4.09 (m, 2H).

Workup

  1. filtrationThe resulting white precipitate was filtered off
  2. concentrationThe filtrates were concentrated
  3. customthe residues purified by column chromatography on silica eluting with saturated ammonia in methanol/dichloromethane (25/75)
  4. additionThe fractions containing the desired product
  5. customevaporated

Sources & evidence

ORD record
ord-fd232c69c90944ada391054ec49e10f5
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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