Hydrochloric Acid → tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-(4-ethoxy-2,4-dioxobutyl)-1,4-oxazepane-4-carboxylate

HRID 1022705Notes

Reaction equation

HRID 1022705 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[C:13]([O:17][C:18]([N:20]1[CH2:26][C@@H:25]([CH2:27][C:28]([OH:30])=O)[C@H:24]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=2)[O:23][CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[CH2:39]([O:41][C:42](=[O:47])[CH2:43]C([O-])=O)[CH3:40].[K+].[Cl-].[Mg+2].[Cl-].Cl>C1COCC1>[Cl:38][C:33]1[CH:32]=[C:31]([C@@H:24]2[O:23][CH2:22][CH2:21][N:20]([C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:19])[CH2:26][C@H:25]2[CH2:27][C:28](=[O:30])[CH2:43][C:42]([O:41][CH2:39][CH3:40])=[O:47])[CH:36]=[CH:35][C:34]=1[Cl:37]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium ChlorideHCID 66976505[(6R,7R)-4-(tert-butoxycarbonyl)-7-(3,4-dichlorophenyl)-1,4-oxazepan-6-yl]acetic acid

Product 1

HCID 66976292tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-(4-ethoxy-2,4-dioxobutyl)-1,4-oxazepane-4-carboxylateYield 87.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

CDI (0.991 g, 6.11 mmol) was added to a solution of [(6R,7R)-4-(tert-butoxycarbonyl)-7-(3,4-dichlorophenyl)-1,4-oxazepan-6-yl]acetic acid (1.9 g, 4.70 mmol) in THF (20 ml), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture were added potassium 3-ethoxy-3-oxopropanoate (0.880 g, 5.17 mmol) and magnesium chloride (0.492 g, 5.17 mmol). The reaction mixture was stirred at 60° C. for 5 hr. To the reaction mixture was added 1 N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (1.959 g).

Workup

  1. stirringThe reaction mixture was stirred at 60° C. for 5 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6cff76a331004cdda7b56db95b053b38
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

Loading…