Water → (7RS)-4-benzyl-7-(3,4-dichlorophenyl)-7-[(4-methoxyphenoxy)methyl]-1,4-oxazepan-3-one

HRID 1022588Notes

Reaction equation

HRID 1022588 reaction equation
[CH2:1]([N:8]([CH2:13][CH2:14][C:15]([C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=1)([OH:26])[CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[C:9](=[O:12])[CH2:10]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].O>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:14][C:15]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=2)([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[O:26][CH2:10][C:9]1=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 23676156Sodium t-butoxideHCID 66976486N-benzyl-2-chloro-N-[(3RS)-3-(3,4-dichlorophenyl)-3-hydroxy-4-(4-methoxyphenoxy)butyl]acetamide

Product 1

HCID 66976203(7RS)-4-benzyl-7-(3,4-dichlorophenyl)-7-[(4-methoxyphenoxy)methyl]-1,4-oxazepan-3-oneYield 87.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-benzyl-2-chloro-N-[(3RS)-3-(3,4-dichlorophenyl)-3-hydroxy-4-(4-methoxyphenoxy)butyl]acetamide (7.41 g) in THF (741 mL) was added sodium tert-butoxide (1.37 g), and the mixture was stirred at 0° C. for 2 hr, and then stirred while warming to room temperature for 14 hr. To the reaction mixture was added water, and the mixture was concentrated. The concentrated residue was diluted with water, and the mixture was extracted with ethyl acetate. The obtained extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (6.02 g).

Workup

  1. stirringstirred
  2. temperaturewhile warming to room temperature for 14 hr
  3. concentrationthe mixture was concentrated
  4. additionThe concentrated residue was diluted with water
  5. extractionthe mixture was extracted with ethyl acetate
  6. extractionThe obtained extract
  7. washwas washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-85eff9a6f75c420cb9b00d12b1b96f97
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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