Triethylamine → tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-{[5-(ethoxycarbonyl)-2-methyl-1,3-thiazol-4-yl]methyl}-1,4-oxazepane-4-carboxylate

HRID 1022711Notes

Reaction equation

HRID 1022711 reaction equation
S(Cl)(Cl)(=O)=O.[Cl:6][C:7]1[CH:8]=[C:9]([C@@H:14]2[O:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][C@H:15]2[CH2:28][C:29](=O)[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:10]=[CH:11][C:12]=1[Cl:13].[C:37]([NH2:40])(=[S:39])[CH3:38].C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C1(C)C=CC=CC=1.C(O)C>[Cl:6][C:7]1[CH:8]=[C:9]([C@@H:14]2[O:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:16][C@H:15]2[CH2:28][C:29]2[N:40]=[C:37]([CH3:38])[S:39][C:30]=2[C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:10]=[CH:11][C:12]=1[Cl:13]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 24648Sulfuryl chlorideHCID 90495Di-tert-butyl dicarbonateHCID 2723949ThioacetamideHCID 66976292tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-(4-ethoxy-2,4-dioxobutyl)-1,4-oxazepane-4-carboxylate

Product 1

HCID 66975856tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-{[5-(ethoxycarbonyl)-2-methyl-1,3-thiazol-4-yl]methyl}-1,4-oxazepane-4-carboxylateYield 64.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

Sulfuryl chloride (0.094 mL, 1.16 mmol) was added to a solution of tert-butyl (6R,7R)-7-(3,4-dichlorophenyl)-6-(4-ethoxy-2,4-dioxobutyl)-1,4-oxazepane-4-carboxylate (500 mg, 1.05 mmol) in toluene (5 mL). The reaction mixture was stirred at room temperature for 45 min, and concentrated under reduced pressure. To the residue were added ethanol (5 ml) and thioacetamide (87 mg, 1.16 mmol), and the mixture was stirred at 80° C. for 1.5 hr. To the reaction mixture were added triethylamine (0.294 mL, 2.11 mmol) and di-tert-butyl dicarbonate (0.291 ml, 1.26 mmol) at room temperature, and the mixture was stirred at room temperature for 30 min, and concentrated under reduced pressure. To the residue was added aqueous sodium hydrogen carbonate solution, 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 (358 mg).

Workup

  1. concentrationconcentrated under reduced pressure
  2. stirringthe mixture was stirred at 80° C. for 1.5 hr
  3. stirringthe mixture was stirred at room temperature for 30 min
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue was added aqueous sodium hydrogen carbonate solution
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3c1529f8a629466da58cc58fcbddf0f7
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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