1,1-Dimethylhydrazine → 4-benzyl-4-(N',N'-dimethylhydrazinocarbonyl)piperidine-1-carboxylic acid tert-butyl ester

HRID 380660Notes

Reaction equation

HRID 380660 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:46][N:47]([CH3:49])[NH2:48].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:14]([NH:48][N:47]([CH3:49])[CH3:46])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 59761,1-DimethylhydrazineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 121510204-Benzyl-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid

Product 1

HCID 206947194-benzyl-4-(N',N'-dimethylhydrazinocarbonyl)piperidine-1-carboxylic acid tert-butyl esterYield 89.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-benzylpiperidine-1,4-dicarboxylic acid 1-tert-butyl ester (0.75 g, 2.35 mmol) (prepared as in Gilligan et al J. Med. Chem. 1994, 364-370) in methylene chloride (10 ml) was added 1-hydroxy-7-azabenzotriazole (0.32 mg, 2.35 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.45 g, 2.35 mmol) and the mixture was stirred for 30 min. Then N′,N′-dimethylhydrazine (0.27 ml, 3.53 mmol) and diisopropylethylamine (0.52 ml, 3.06 mmol) was added and the mixture was stirred for 2 days. Methylene chloride (100 ml) was added and the mixture was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml), dried (MgSO4), filtered and concentrated in vacuo. The obtained oil was chromatographed on silica (40 g) with heptane/ethyl acetate (1:2) to give 0.76 g of 4-benzyl-4-(N′,N′-dimethylhydrazinocarbonyl)piperidine-1-carboxylic acid tert-butyl ester as a colorless oil.

Workup

  1. stirringthe mixture was stirred for 2 days
  2. washthe mixture was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe obtained oil was chromatographed on silica (40 g) with heptane/ethyl acetate (1:2)

Sources & evidence

ORD record
ord-f5c0fbab1bf34f209b25058fb216c10f
Source dataset
uspto-grants-2001_10
Patent number
US06303620B1

Reaction notes

Loading…