HCID 57589905, compound → HCID 86610740, compound

HRID 1783393Notes

Reaction equation

HRID 1783393 reaction equation
C(OC(=O)N[C@@H]1CC=CCN(CC2C=CC(OC)=CC=2OC)C1=O)(C)(C)C.[C:28]([O:32][C:33](=[O:55])[NH:34][C@@H:35]1[CH2:41][CH2:40][C:39](=[O:42])[CH2:38][N:37]([CH2:43][C:44]2[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][C:45]=2[O:52][CH3:53])[C:36]1=[O:54])([CH3:31])([CH3:30])[CH3:29].[C:56]([O:60][C:61](=[O:83])[NH:62][C@@H:63]1[CH2:69][C:68](=[O:70])[CH2:67][CH2:66][N:65]([CH2:71][C:72]2[CH:77]=[CH:76][C:75]([O:78][CH3:79])=[CH:74][C:73]=2[O:80][CH3:81])[C:64]1=[O:82])([CH3:59])([CH3:58])[CH3:57]>CN(C=O)C.O.O>[C:56]([O:60][C:61](=[O:83])[NH:62][C@@H:63]1[CH2:69][C:68](=[O:70])[CH2:67][CH2:66][N:65]([CH2:71][C:72]2[CH:77]=[CH:76][C:75]([O:78][CH3:79])=[CH:74][C:73]=2[O:80][CH3:81])[C:64]1=[O:82])([CH3:59])([CH3:57])[CH3:58].[C:28]([O:32][C:33](=[O:55])[NH:34][C@@H:35]1[CH2:41][CH2:40][C:39](=[O:42])[CH2:38][N:37]([CH2:43][C:44]2[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][C:45]=2[O:52][CH3:53])[C:36]1=[O:54])([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 3

HCID 57589905HCID 57589905, compoundHCID 57589911HCID 57589911, compoundHCID 57589916HCID 57589916, compound

Product 1

HCID 86610740HCID 86610740, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
50 °C

Procedure

[(R)-1-(2,4-Dimethoxy-benzyl)-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-yl]-carbamic acid tert-butyl ester (5.4 g, 14.3 mmol) was dissolved in DMF/water (10:1 v/v) and then Pd(II)Cl2 (1 g, 5.7 mmol) and Cu(I)Cl (7.2 g, 72.4 mmol) were added. The reaction mixture was evacuated and saturated with O2 and then heated at 50° C. for 48 h. Further additions of Pd(II)Cl2 (3× 0.4 equiv.) were used during the reaction. The reaction mixture was diluted with water (400 ml) and filtered over Celite. The filtrate was extracted with ethyl acetate (5×) and the combined organic extracts were washed with NaHCO3 solution, 1 M KHSO4 solution, brine, dried (MgSO4.2H2O), filtered, concentrated under reduce pressure and purified over silica gel (ethyl acetate/n-heptane 1:2->1:1) to yield a mixture of [(R)-1-(2,4-dimethoxy-benzyl)-2,6-dioxo-azepan-3-yl]-carbamic acid tert-butyl ester and [(R)-1-(2,4-dimethoxy-benzyl)-2,5-dioxo-azepan-3-yl]-carbamic acid tert-butyl ester in a 1:2 ratio: white solid 3.8 g (67%);

Workup

  1. customThe reaction mixture was evacuated and saturated with O2
  2. filtrationfiltered over Celite
  3. extractionThe filtrate was extracted with ethyl acetate (5×)
  4. washthe combined organic extracts were washed with NaHCO3 solution, 1 M KHSO4 solution, brine
  5. dry with materialdried (MgSO4.2H2O)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified over silica gel (ethyl acetate/n-heptane 1:2->1:1)
  9. customto yield

Sources & evidence

ORD record
ord-dcedabcac5534c418b6e92f382b85b8e
Source dataset
uspto-grants-2009_03
Patent number
US07501406B2

Reaction notes

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