Hydrochloric Acid → 2-(4-Bromo-2,6-dichloro-benzyl)-2-aza-spiro[4.5]decan-1-one

HRID 2427474Notes

Reaction equation

HRID 2427474 reaction equation
[C:1]1(=[O:11])[C:5]2([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]2)[CH2:4][CH2:3][NH:2]1.[H-].[Na+].[Br:14][C:15]1[CH:16]=[C:17]([Cl:24])[C:18]([CH2:22]Br)=[C:19]([Cl:21])[CH:20]=1.Cl>CN(C=O)C.C(OCC)C>[Br:14][C:15]1[CH:16]=[C:17]([Cl:24])[C:18]([CH2:22][N:2]2[CH2:3][CH2:4][C:5]3([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]3)[C:1]2=[O:11])=[C:19]([Cl:21])[CH:20]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 250672652-Azaspiro(4.5)decan-1-oneHCID 594744985-Bromo-2-(bromomethyl)-1,3-dichlorobenzene

Product 1

HCID 248637462-(4-Bromo-2,6-dichloro-benzyl)-2-aza-spiro[4.5]decan-1-oneYield 73.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Treat a solution of 2-aza-spiro[4.5]decan-1-one (0.138 g, 0.901 mmol) in DMF (5 mL) with 60% sodium hydride (0.054 g, 1.35 mmol) and stir at room temperature for 15 minutes under N2. Cool the reaction to 0° C., treat with 5-bromo-2-(bromomethyl)-1,3-dichlorobenzene (0.316 g, 0.991 mmol), and stir for 15 minutes at 0° C. Warm to room temperature and stir for 2 hours under N2. Acidify the reaction with 1 N HCl. Dilute with diethyl ether and wash with water. Dry the organic layer with Na2SO4 and remove the solvent in vacuo to afford crude product. Purify with a 0 to 100% ethyl acetate in hexanes gradient on silica gel to afford 0.258 g (73%) of the titled product. Rf=0.24 (3/1 ethyl acetate/hexanes). MS (m/z): 392 (M+).

Workup

  1. temperatureCool
  2. customthe reaction to 0° C.
  3. stirringstir for 15 minutes at 0° C
  4. temperatureWarm to room temperature
  5. stirringstir for 2 hours under N2
  6. washwash with water
  7. dry with materialDry the organic layer with Na2SO4
  8. customremove the solvent in vacuo
  9. customto afford crude product
  10. customPurify with a 0 to 100% ethyl acetate in hexanes gradient on silica gel

Sources & evidence

ORD record
ord-2a2740dc51b949448343ea9ea90ed22e
Source dataset
uspto-grants-2011_06
Patent number
US07968585B2

Reaction notes

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