Cesium carbonate → Ethyl 10-(((benzyloxy)carbonyl)amino)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylate

HRID 1093076Notes

Reaction equation

HRID 1093076 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1([C:24]2[NH:25][CH2:26][C:27]([O:35]S(C)(=O)=O)=[C:28]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[N:29]=2)[CH2:17][CH2:16][CH:15]([CH2:18]OS(C)(=O)=O)[CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-:41].[Cs+].[Cs+]>CN(C=O)C>[CH2:1]([O:8][C:9]([NH:11][C:12]12[CH2:13][CH2:14][CH:15]([CH2:16][CH2:17]1)[CH2:18][N:25]1[C:26](=[O:41])[C:27]([OH:35])=[C:28]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[N:29]=[C:24]21)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 178470087HCID 178470087, compound

Product 1

HCID 57904801Ethyl 10-(((benzyloxy)carbonyl)amino)-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylateYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of ethyl 2-(1-(benzyloxycarbonylamino)-4-((methylsulfonyloxy)methyl)cyclohexyl)-5-(methylsulfonyloxy)-1,6-dihydropyrimidine-4-carboxylate (2.25 g, 3.74 mmol) and cesium carbonate (1.22 g, 3.74 mmol) in DMF (40 mL) was heated at 60° C. for 18 h. The reaction mixture was then cooled and concentrated in vacuo. The residue was taken up in ethyl acetate (200 mL) and extracted with 0.2 M aq. NaOH (3×50 mL). The combined aqueous phase was washed with ethyl acetate (250 mL). The aqueous layer was then acidified with conc. HCl and extracted with CH2Cl2 (3×100 mL). The CH2Cl2 extracts were dried (Na2SO4), filtered and concentrated to afford the title compound as a brown solid (400 mg). 1H NMR (500 MHz, CDCl3) δ: 10.81 (s, 1H), 7.29-7.36 (m, 6H), 5.29 (s, 1H), 5.10 (s, 2H), 4.41 (q, 2H, J=7.27 Hz), 4.13 (d, 2H, J=3.66 Hz), 2.43-2.47 (m, 2H), 1.94-2.02 9 m, 2H), 1.79-1.85 (m, 2H), 1.65-1.72 (m, 2H), 1.40 (t, 3H, J=7.17). LCMS (M+H)=428.26.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. concentrationconcentrated in vacuo
  3. extractionextracted with 0.2 M aq. NaOH (3×50 mL)
  4. washThe combined aqueous phase was washed with ethyl acetate (250 mL)
  5. extractionextracted with CH2Cl2 (3×100 mL)
  6. dry with materialThe CH2Cl2 extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-920be62e82ff432ab6393e37820f666a
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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