Sodium hydride → HCID 68944467, compound

HRID 659090Notes

Reaction equation

HRID 659090 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]Br>CN(C=O)C>[C:18]([O:17][C:15](=[O:16])[N:14]([CH:11]1[CH2:12][CH2:13][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9][CH2:10]1)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][Br:24])([CH3:21])([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 783091,7-DibromoheptaneHCID 44386181-Benzyl-4-(N-Boc-amino)piperidine

Product 1

HCID 68944467HCID 68944467, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a chilled solution of 1-benzyl-4-tert-butoxycarbonylaminopiperidine (6.8 g, 23.4 mmol) in DMF (200 mL) was added sodium hydride (0.6 g, 60% dispersion in mineral oil). After 30 min, 1,7-dibromoheptane was added (12 mL) and the reaction mixture was stirred for 24 h. Another portion of sodium hydride (0.6 g, 60% dispersion in mineral oil) was added and the reaction mixture was stirred for 18 h. The DMF was removed in vacuo and the residue extracted with dichloromethane and 1 N HCl (3×). The organic phase was washed with saturated brine, dried over sodium sulfate, filtered and concentrated to give 18.5 g of the crude intermediate. This crude product was purified by silica gel column chromatography, eluting with 1% methanol in dichloromethane. The appropriate fractions were combined and concentrated to afford 4.7 g of the title intermediate (85% pure by HPLC, MS and NMR), which was used without further purification.

Workup

  1. stirringthe reaction mixture was stirred for 18 h
  2. customThe DMF was removed in vacuo
  3. extractionthe residue extracted with dichloromethane and 1 N HCl (3×)
  4. washThe organic phase was washed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give 18.5 g of the crude intermediate
  9. customThis crude product was purified by silica gel column chromatography
  10. washeluting with 1% methanol in dichloromethane
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-2648f03390654f488bf17808b5341913
Source dataset
uspto-grants-2011_12
Patent number
US08080565B2

Reaction notes

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