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

HRID 655515Notes

Reaction equation

HRID 655515 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>CN(C)C(=O)C.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 N,N-dimethylacetamide 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 [49.6 g (250 mmol, 6.3 eq.) 1-(3-chloropropyl)piperidine hydrochloride were dissolved in 262 ml of 1 M aq. sodium hydroxide solution and extracted with toluene (200 ml). The organic phase was dried over Na2SO4]. The reaction was warmed up to room temperature and stirred over night. After 2 h at 50° C. and cooling to room temperature, the reaction was neutralized with water (50 ml), evaporated and then dissolved in sat. aq. sodium hydrogencarbonate solution/diethyl ether. After reextraction with diethyl ether, 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 room temperature
  6. customevaporated
  7. dissolutiondissolved in sat. aq. sodium hydrogencarbonate solution/diethyl ether
  8. dry with materialAfter reextraction with diethyl ether, the organic phase was dried (Na2SO4)
  9. customevaporated
  10. customcrystallized from pentane

Sources & evidence

ORD record
ord-f14000ca8a3345c3b81b3335e7cae1c3
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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