Methyl 2,2-difluoro-2-(fluorosulfonyl)acetate → tert-butyl 2,2-difluoro-2',3'-dihydro-1'H-spiro[cyclopropane-1,4'-quinoline]-1'-carbamate

HRID 551829Notes

Reaction equation

HRID 551829 reaction equation
[CH2:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:4][CH2:3]1.FS([C:24]([F:30])([F:29])C(OC)=O)(=O)=O>[F-].[Na+].C1(C)C=CC=CC=1>[F:29][C:24]1([F:30])[C:2]2([C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:4][CH2:3]2)[CH2:1]1

Participants

5

Reactant 2

HCID 547667Methyl 2,2-difluoro-2-(fluorosulfonyl)acetateHCID 67188896tert-butyl 4-methylene-3,4-dihydro-2H-quinoline-1-carbamate

Product 1

HCID 67192015tert-butyl 2,2-difluoro-2',3'-dihydro-1'H-spiro[cyclopropane-1,4'-quinoline]-1'-carbamateYield 70.2%

Reagents, catalysts & solvents 2

HCID 5235Sodium FluorideCatalystHCID 1140TolueneSolvent

Procedure

0.275 g of tert-butyl 4-methylene-3,4-dihydro-2H-quinoline-1-carbamate, 0.0028 g of sodium fluoride and 1.5 ml of toluene are placed in a 10 ml round-bottomed flask equipped with a magnetic stirrer and placed under an inert atmosphere. The reaction mixture is heated at reflux for 1 h. 0.449 g of methyl fluorosulfonyldifluoroacetate is subsequently added and the reaction mixture is heated at reflux for 2 h, filtered through celite and then concentrated under reduced pressure. The residue is chromatographed twice on silica gel eluted with dichloromethane. 0.23 g of tert-butyl 2,2-difluoro-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-quinoline]-1′-carbamate is obtained.

Workup

  1. customequipped with a magnetic stirrer
  2. temperatureThe reaction mixture is heated
  3. temperatureat reflux for 1 h
  4. temperaturethe reaction mixture is heated
  5. temperatureat reflux for 2 h
  6. filtrationfiltered through celite
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is chromatographed twice on silica gel
  9. washeluted with dichloromethane

Sources & evidence

ORD record
ord-32699d2a62a5418e992c2b571923fbce
Source dataset
uspto-grants-2011_05
Patent number
US07947834B2

Reaction notes

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