Dimethylformamide → tert-Butyl 4-{3-[4-(4-fluorobenzyl)-3-oxopiperazin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 2109851Notes

Reaction equation

HRID 2109851 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([CH3:18])C(O)=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.[F:41][C:42]1[CH:55]=[CH:54][C:45]([CH2:46][N:47]2[CH2:52][CH2:51][NH:50][CH2:49][C:48]2=[O:53])=[CH:44][CH:43]=1.CN([CH:59]=[O:60])C>>[F:41][C:42]1[CH:55]=[CH:54][C:45]([CH2:46][N:47]2[CH2:52][CH2:51][N:50]([C:59](=[O:60])[CH2:18][CH2:14][CH:11]3[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:13][CH2:12]3)[CH2:49][C:48]2=[O:53])=[CH:44][CH:43]=1

Participants

6

Reactant 5

HCID 6228Dimethylformamide2×HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 177818912-[1-(Tert-butoxycarbonyl)piperidin-4-yl]propanoic acidHCID 185386381-(4-Fluorobenzyl)piperazin-2-one

Product 1

HCID 57634639tert-Butyl 4-{3-[4-(4-fluorobenzyl)-3-oxopiperazin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

Procedure

To a solution of 1-boc-piperidin-4-ylpropionic acid (1.20 g, 4.7 mmol, Astatech) in DMF (10 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.16 g, 6.1 mmol) and 1-hydroxy-7-azabenzotriazole (0.83 g, 6.1 mmol) were added and the solution was stirred at room temperature for 30 min. To the resultant solution, a solution of 1-(4-fluorobenzyl)piperazin-2-one (1.07 g, 5.1 mmol, see Example 31, Steps 5-8) in DMF (2 mL) was added and the mixture was stirred for two hours. The product mixture was concentrated under vacuum, and the residue partitioned between water and ethyl acetate. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (ISCO column, 120 g silica gel) eluting with a 0-6% MeOH/CHCl3 gradient over 40 min. Collection and concentration of appropriate fractions provided the coupled product as a white solid.

Workup

  1. stirringthe mixture was stirred for two hours
  2. concentrationThe product mixture was concentrated under vacuum
  3. customthe residue partitioned between water and ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography (ISCO column, 120 g silica gel)
  9. washeluting with a 0-6% MeOH/CHCl3 gradient over 40 min
  10. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-ae165f3ae2584ab292a1bdd94fcc904e
Source dataset
uspto-grants-2009_04
Patent number
US07517532B2

Reaction notes

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