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

HRID 2427469Notes

Reaction equation

HRID 2427469 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[CH2:15][C:16]1[C:21]([Cl:22])=[CH:20][C:19]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:18][C:17]=1[Cl:31].Cl>CN(C=O)C.C(OCC)C>[CH2:24]([O:23][C:19]1[CH:18]=[C:17]([Cl:31])[C:16]([CH2:15][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:21]([Cl:22])[CH:20]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 250672652-Azaspiro(4.5)decan-1-oneHCID 592994282-Bromomethyl-1,3-dichloro-5-benzyloxy-benzene

Product 1

HCID 671483482-(4-Benzyloxy-2,6-dichloro-benzyl)-2-aza-spiro[4.5]decan-1-oneYield 90.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Treat a solution of 2-aza-spiro[4.5]decan-1-one (0.50 g, 3.26 mmol) in DMF (8 mL) with 60% sodium hydride (0.20 g, 5.0 mmol) and stir at room temperature for 20 minutes under N2. Cool the reaction to 0° C., treat with 2-bromomethyl-1,3-dichloro-5-benzyloxy-benzene (1.24 g, 3.58 mmol), 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 the reaction with diethyl ether, and then 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 1.23 g (90%) of the titled product. Rf=0.23 (3/1 ethyl acetate/hexanes). MS (m/z): 418 (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. additiondilute
  7. washwash with water
  8. dry with materialDry the organic layer with Na2SO4
  9. customremove the solvent in vacuo
  10. customto afford crude product
  11. customPurify with a 0 to 100% ethyl acetate in hexanes gradient on silica gel

Sources & evidence

ORD record
ord-bf948a3e529e45898595d7df9fe9708c
Source dataset
uspto-grants-2011_06
Patent number
US07968585B2

Reaction notes

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