Sodium hydride → 5-Oxo-4-(3-piperidin-1-yl-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 1867358Notes

Reaction equation

HRID 1867358 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12](=[O:15])[NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[CH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.Cl.ClCCCN1CCCCC1>CC(N(C)C)=O.C1(C)C=CC=CC=1.[OH-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]([CH2:19][CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 79624N-(3-chloropropyl)piperidine hydrochlorideHCID 79625Piperidine, 1-(3-chloropropyl)-HCID 226177365-Oxo-(1,4)diazepane-1-carboxylic acid tert-butyl ester

Product 1

HCID 667834965-Oxo-4-(3-piperidin-1-yl-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 90%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 14798Sodium HydroxideSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 8.52 g (39.75 mmol) of 5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester in 200 ml of DMA was treated at 0° C. with 2.60 g (59.62 mmol) of NaH (55% in oil) in small portions. The reaction was stirred 1 h at this temperature, then the free 1-(3-chloropropyl)piperidine in 200 ml toluene was dropped in (49.62 g (250.42 mmol, 6.3 eq.) 1-(3-chloropropyl)piperidine hydrochloride were dissolved in 262 ml of 1N NaOH and extracted with toluene (200 ml). The organic phase was dried over Na2SO4). The reaction was warmed up to RT and stirred over night. After 2 h at 50° C. and cooling to RT, the reaction was neutralized with water (50 ml), evaporated and then dissolved in aqueous saturated NaHCO3/Et2O. After reextraction with Et2O, the organic phase was dried (Na2SO4), evaporated and crystallized from pentane to yield 12.08 g (90%) of the title compound as white crystals. MS: 340.2 (MH+).

Workup

  1. extractionextracted with toluene (200 ml)
  2. dry with materialThe organic phase was dried over Na2SO4)
  3. stirringstirred over night
  4. waitAfter 2 h at 50° C.
  5. temperaturecooling to RT
  6. customevaporated
  7. dissolutiondissolved in aqueous saturated NaHCO3/Et2O
  8. dry with materialAfter reextraction with Et2O, the organic phase was dried (Na2SO4)
  9. customevaporated
  10. customcrystallized from pentane

Sources & evidence

ORD record
ord-2207ef359e0449b08ca9e529b158ec58
Source dataset
uspto-grants-2009_12
Patent number
US07632829B2

Reaction notes

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