Chloroacetyl chloride → 4-Benzyl-6-(4-octyloxy-phenyl)-morpholin-3-one

HRID 920536Notes

Reaction equation

HRID 920536 reaction equation
[CH2:1]([NH:8][CH2:9][CH:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:14][CH:13]=1)[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.Cl[CH2:35][C:36](Cl)=[O:37].[OH-].[K+]>C(Cl)Cl>[CH2:1]([N:8]1[CH2:9][CH:10]([C:12]2[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[CH:16][CH:17]=2)[O:11][CH2:35][C:36]1=[O:37])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 670324692-Benzylamino-1-(4-octyloxy-phenyl)ethanol

Product 1

HCID 670324644-Benzyl-6-(4-octyloxy-phenyl)-morpholin-3-oneYield 89.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-benzylamino-1-(4-octyloxy-phenyl)-ethanol (22.50 g; 63.3 mmol) and Et3N (9.7 mL; 69.6 mmol) in CH2Cl2 (500 mL) was added dropwise a solution of chloroacetyl chloride (5.5 mL; 69.6 mmol) in CH2Cl2 (25 mL), at 0° C. After 1 hour at 0° C. the reaction mixture was quenched with 1M aqueous HCl (200 mL). The layers were separated and the organic layer washed with a 5% aqueous NaHCO3 solution, dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in 2-propanol (250 mL) and KOH (4.26 g; 76 mmol) was added. The resulting mixture was stirred at RT for 1 hour and subsequently concentrated in vacuo. The crude product was partitioned between EtOAc and 0.5 M aqueous HCl. The layers were separated and the organic layer was washed with 5% aqueous NaHCO3 solution, dried (Na2SO4) and evaporated in vacuo to afford 4-benzyl-6-(4-octyloxy-phenyl)-morpholin-3-one (22.30 g) which was used as such in the next step.

Workup

  1. customat 0° C
  2. customAfter 1 hour at 0° C. the reaction mixture was quenched with 1M aqueous HCl (200 mL)
  3. customThe layers were separated
  4. washthe organic layer washed with a 5% aqueous NaHCO3 solution
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in 2-propanol (250 mL)
  8. concentrationsubsequently concentrated in vacuo
  9. customThe crude product was partitioned between EtOAc and 0.5 M aqueous HCl
  10. customThe layers were separated
  11. washthe organic layer was washed with 5% aqueous NaHCO3 solution
  12. dry with materialdried (Na2SO4)
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-8eb1f517c8be4ba29d7b5207509a37d1
Source dataset
uspto-grants-2016_03
Patent number
US09273017B2

Reaction notes

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