Chloroacetyl chloride → (S)-6-(4-bromophenyl)-4-((R)-1-phenylethyl)-1,4-oxazepan-3-one

HRID 515462Notes

Reaction equation

HRID 515462 reaction equation
[C:1]1([C@H:7]([NH:9][CH2:10][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=2)[CH2:12][OH:13])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl[CH2:29][C:30](Cl)=[O:31].[OH-].[K+]>ClCCl>[Br:20][C:17]1[CH:16]=[CH:15][C:14]([C@@H:11]2[CH2:12][O:13][CH2:29][C:30](=[O:31])[N:9]([C@@H:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH3:8])[CH2:10]2)=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 672813523-((R)-1-phenylethylamino)-2-(4-bromophenyl)propan-1-ol

Product 1

HCID 67282262(S)-6-(4-bromophenyl)-4-((R)-1-phenylethyl)-1,4-oxazepan-3-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of diastereopure 3-((R)-1-phenylethylamino)-2-(4-bromophenyl)propan-1-ol (2.40 g, 7.18 mmol) in dichloromethane (22.0 ml) was added triethylamine (0.799 g, 7.90 mmol) and chloroacetyl chloride (0.892 g, 7.90 mmol) at 0° C. The mixture was stirred at 0° C. for one hour. The reaction mixture was partitioned between 0.5N—HCl and dichloromethane, and the organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. To the residue dissolved into 2-propanol (48 ml) was added potassium hydroxide (805 mg, 14.4 mmol) at 0° C. The mixture was stirred at 0° C. for 3 hours and partitioned between saturated ammonium chloride solution and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=7/3) to afford (S)-6-(4-bromophenyl)-4-((R)-1-phenylethyl)-1,4-oxazepan-3-one as white solid (2.42 g, 90 W. An analytical sample for X-ray was obtained by crystallization from dichloromethane-hexane and the absolute configuration of 6-position was found to be the (S)-configuration.

Workup

  1. customThe reaction mixture was partitioned between 0.5N—HCl and dichloromethane
  2. washthe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionTo the residue dissolved into 2-propanol (48 ml)
  6. stirringThe mixture was stirred at 0° C. for 3 hours
  7. custompartitioned between saturated ammonium chloride solution and ethyl acetate
  8. washThe organic layer was washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel column chromatography (eluant: hexane/ethyl acetate=7/3)

Sources & evidence

ORD record
ord-e090a84f71c04516ba85b5d76d656728
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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