Cesium carbonate → 5-[4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-quinolin-7-yloxymethyl]-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl ester

HRID 455795Notes

Reaction equation

HRID 455795 reaction equation
[F:1][C:2]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([OH:17])=[C:12]([O:15][CH3:16])[CH:13]=2)[N:8]=[CH:7][CH:6]=1.CC(N(C)C)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:37]([O:44][C:45]([N:47]1[CH2:51][CH:50]2[CH2:52][CH:53]([CH2:55]OS(C)(=O)=O)[CH2:54][CH:49]2[CH2:48]1)=[O:46])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O>[CH2:37]([O:44][C:45]([N:47]1[CH2:48][CH:49]2[CH2:54][CH:53]([CH2:55][O:17][C:11]3[CH:10]=[C:9]4[C:14]([C:5]([O:4][C:3]5[CH:18]=[CH:19][C:20]([N+:22]([O-:24])=[O:23])=[CH:21][C:2]=5[F:1])=[CH:6][CH:7]=[N:8]4)=[CH:13][C:12]=3[O:15][CH3:16])[CH2:52][CH:50]2[CH2:51]1)=[O:46])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 31374DimethylacetamideHCID 578103315-Methanesulfonyloxymethyl-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl esterHCID 1361757014-(2-Fluoro-4-nitrophenoxy)-7-hydroxy-6-methoxyquinoline

Product 1

HCID 578102065-[4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-quinolin-7-yloxymethyl]-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-quinolin-7-ol (2.74 g, 6.7 mmol, 1.0 eq.), DMA (30 ml) and cesium carbonate (6.6 g, 20.2 mmol, 3.0 eq). The mixture was stirred at room temperature for 30 minutes at which time 5-methanesulfonyloxymethyl-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl ester (2.6 g, 7.3 mmol, 1.1 eq) was added. The reaction was heated to 75° C. and allowed to stir overnight. After allowing the reaction to cool to room temperature the reaction was poured into water. The solid was filtered and was then dissolved in EtOAc and washed 2× water, 1× brine and dried over NaSO4. The solvent was removed to yield 5-[4-(2-Fluoro-4-nitro-phenoxy)-6-methoxy-quinolin-7-yloxymethyl]-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid benzyl ester as a cream solid (3.7 g, 94% yield). 1H NMR (400 MHz, CDCl3): 8.55 (d, 1H), 8.15 (d, 1H), 8.09 (d, 1H), 7.32 (m, 8H), 6.52 (d, 1H), 5.11 (d, 2H), 4.13 (d, 2H), 3.95 (s, 3H), 3.57 (m, 2H), 3.43 (m, 2H), 2.93 (m, 3H), 2.16 (m, 2H), 1.39 (m, 2H); MS (EI) for C32H30FN3O7: 588 (M+H+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. additionwas added
  3. customthe reaction
  4. temperatureto cool to room temperature the reaction
  5. filtrationThe solid was filtered
  6. dissolutionwas then dissolved in EtOAc
  7. washwashed 2× water, 1× brine
  8. dry with materialdried over NaSO4
  9. customThe solvent was removed

Sources & evidence

ORD record
ord-b110083d240446d294675488188abe69
Source dataset
uspto-grants-2013_07
Patent number
US08497284B2

Reaction notes

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