Diethyl azodicarboxylate → N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N',N''-tri-Boc-guanidine

HRID 2199565Notes

Reaction equation

HRID 2199565 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9][CH2:10]O)[CH2:4][CH2:3]1.[C:12]([NH:19][C:20]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[N:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([CH2:8][CH2:9][CH2:10][N:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:20]([NH:29][C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])=[N:19][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 5462977Diethyl azodicarboxylateHCID 10570451N,N',N''-Tri-Boc-guanidineHCID 155406773-(1-Methylpiperidin-4-yl)propan-1-ol

Product 1

HCID 68526405N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N',N''-tri-Boc-guanidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 100 mL, 3-neck, round bottom flask were added 3-(1-methyl -piperidin-4-yl)-propan-1-ol (1.91 g, 0.012 mol), Polymer Labs (Varian) PL-TPP resin (9.83 g, 0.014 mol), N,N′,N″-tri-Boc-guanidine (4.36 g, 0.012 mol) and THF (anhydrous, 100 mL). The resultant mixture was stirred and cooled to 2° C., at which time DEAD (2.53 g, 0.014 mol) was added drop wise over 10 min. Upon completion of addition, the flask was warmed to room temperature, aged for 4 h and filtered to remove the resin bound oxide. The resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL). The filtrates were combined, extracted with saturated aqueous NaHCO3 (2×25 mL), dried over anhydrous MgSO4, filtered and concentrated. The resultant residue was triturated in hot ethanol (25 mL), cooled to room temperature and filtered. The filtrate was concentrated to yield N-[3-(1-methylpiperidin-4-yl)-propyl]-N,N′,N″-tri-Boc-guanidine.

Workup

  1. additionwas added drop wise over 10 min
  2. additionUpon completion of addition
  3. filtrationfiltered
  4. customto remove the resin
  5. washThe resultant cake was rinsed with THF (25 mL) and heptane (2×25 mL)
  6. extractionextracted with saturated aqueous NaHCO3 (2×25 mL)
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resultant residue was triturated in hot ethanol (25 mL)
  11. temperaturecooled to room temperature
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-4ae8ee25e19d49009718cb9734a69f57
Source dataset
uspto-grants-2016_06
Patent number
US09359327B2

Reaction notes

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