Cesium carbonate → Methyl (2S,4R)-4-[(6-bromo-7-methoxy-2-oxo-1,2-dihydroquinolin-4-yl)oxy]-1-[(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl]pyrrolidine-2-carboxylate

HRID 1924384Notes

Reaction equation

HRID 1924384 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[NH:8][C:7](=[O:14])[CH:6]=[C:5]2[OH:15].BrC1C=CC(S(O[C@@H:27]2[CH2:31][N:30]([C:32](=[O:48])[C@@H:33]([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)[C@H:29]([C:49]([O:51][CH3:52])=[O:50])[CH2:28]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[NH:8][C:7](=[O:14])[CH:6]=[C:5]2[O:15][C@H:27]1[CH2:31][N:30]([C:32](=[O:48])[C@@H:33]([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[C@H:29]([C:49]([O:51][CH3:52])=[O:50])[CH2:28]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 592798516-Bromo-4-hydroxy-7-methoxyquinolin-2(1H)-oneHCID 86635058Methyl (2S,4S)-4-[((4-bromophenyl)sulfonyl)oxy]-1-[(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl]pyrrolidine-2-carboxylate

Product 1

HCID 86635057Methyl (2S,4R)-4-[(6-bromo-7-methoxy-2-oxo-1,2-dihydroquinolin-4-yl)oxy]-1-[(2S)-2-[(tert-butoxycarbonyl)amino]-2-cyclohexylacetyl]pyrrolidine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

To a 0.27 M solution of hydroxyl-quinolinone from Step 3 (1 eq.) and brosylate from Step 2 (1 eq.) in N-methyl-2-pyrrolidinone was added cesium carbonate (1.5 eq.) and the resulting mixture was heated at 60° C. for 16 h. The mixture was cooled to RT and partitioned between water and EtOAc. The organic phase was washed with brine, dried (Na2SO4) and the volatiles were removed under reduced pressure. The residue was purified by SiO2 gel chromatography (eluting with 50% EtOAc/Hex and then 0-5% MeOH/DCM) to yield the title compound. MS (ES+) C29H38BrN3O8 requires: 637. Found: 636, 638 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. custompartitioned between water and EtOAc
  3. washThe organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. customthe volatiles were removed under reduced pressure
  6. customThe residue was purified by SiO2 gel chromatography (
  7. washeluting with 50% EtOAc/Hex

Sources & evidence

ORD record
ord-abbdd2c4838e40278a87aa33a40e60a7
Source dataset
uspto-grants-2012_05
Patent number
US08178520B2

Reaction notes

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