1,2-Dichloroethane → (R)-methyl 1-((S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoyl)piperidine-2-carboxylate

HRID 529491Notes

Reaction equation

HRID 529491 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]1[C:32]([O:34][CH3:35])=[O:33].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl.O>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]1[C:32]([O:34][CH3:35])=[O:33])=[O:15])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 2756240L-N-Cbz-3-N-Boc-Amino-alanineHCID 49759143methyl (2R)-piperidine-2-carboxylate hydrochloride

Product 1

HCID 68292412(R)-methyl 1-((S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoyl)piperidine-2-carboxylateYield 69.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoic acid (2.26 g, 6.68 mmol) in DCM (50 mL) was added (R)-methyl piperidine-2-carboxylate HCl salt (1.00 g, 5.57 mmol), followed by EDC (1.60 g, 8.35 mmol), HOBT (1.71 g, 11.1 mmol), and TEA (2.33 mL, 16.7 mmol). The reaction mixture was stirred at rt for 6 hr. The reaction mixture was diluted with water and extracted with EtOAc (2×30 mL). The combined EtOAc layers were washed with water and saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 30-70% EtOAc/Hex to give (R)-methyl 1-((S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanoyl)piperidine-2-carboxylate (1.80 g, 3.88 mmol, 69.8% yield) as a white foam. Anal. Calcd. for C23H33N3O7 m/z 463.5. found: 464.3 (M+H)+.

Workup

  1. extractionextracted with EtOAc (2×30 mL)
  2. washThe combined EtOAc layers were washed with water and saturated aqueous NaCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified
  7. washeluting with a gradient of 30-70% EtOAc/Hex

Sources & evidence

ORD record
ord-169f628cafc5417dab8706ddc593e920
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

Loading…