Cesium carbonate → (cis)-Benzyl 3-fluoro-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)pyrrolidine-1-carboxylate

HRID 1095680Notes

Reaction equation

HRID 1095680 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[C:18]([OH:25])[CH:19]=[CH:20][CH:21]=4)[N:16]=3)=[CH:13][N:14]=[C:8]2[CH:7]=1.[F:26][C@H:27]1[C@H:31](OS(C)(=O)=O)[CH2:30][N:29]([C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])[CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[F:26][C@H:27]1[C@@H:31]([O:25][C:18]2[CH:19]=[CH:20][CH:21]=[C:22]3[C:17]=2[N:16]=[C:15]([C:12]2[N:9]4[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:7][C:8]4=[N:14][CH:13]=2)[CH:24]=[CH:23]3)[CH2:30][N:29]([C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])[CH2:28]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 66781369HCID 66781369, compoundHCID 131077573(trans)-Benzyl 3-fluoro-4-(methylsulfonyloxy)pyrrolidine-1-carboxylate

Product 1

HCID 131729509(cis)-Benzyl 3-fluoro-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol (1.75 g, 5.22 mmol), (trans)-benzyl 3-fluoro-4-(methylsulfonyloxy)pyrrolidine-1-carboxylate (1.99 g, 6.3 mmol) and cesium carbonate (3.40 g, 10.4 mmol) were added to a sealed tube containing dimethylacetamide and heated to 100° C. overnight with stirring. The dimethylacetamide was removed under vacuum concentration and heat, chloroform was added, and this organic phase was gently washed with water. The combined organic layers were dried over MgSO4, filtered and evaporated. The crude material was purified on silica gel using a 6% solution of ammonium hydroxide in methanol and dichloromethane to yield three major products which could not be separated further by column purification (starting quinoline phenol, product and unidentified by-product). MS APCI (+) m/z 557.3 (M+1) detected. This crude material was taken directly on to the deprotection step.

Workup

  1. customThe dimethylacetamide was removed under vacuum concentration
  2. temperatureheat
  3. additionchloroform was added
  4. washthis organic phase was gently washed with water
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude material was purified on silica gel using a 6% solution of ammonium hydroxide in methanol and dichloromethane
  9. customto yield three major products which could not
  10. custombe separated further by column purification (starting quinoline phenol, product and unidentified by-product)

Sources & evidence

ORD record
ord-c3715ad3576440ceb9282b2f7ab69c67
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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