2,2-Difluoro-2-(fluorosulfonyl)acetic acid → benzyl 6'-bromo-4-(difluoromethoxy)spiro[cyclohexane-1,2'-inden]-1'(3'H)-one

HRID 1503415Notes

Reaction equation

HRID 1503415 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]3)[C:8]2=[O:11])=[CH:4][CH:3]=1.FS([C:22](C(O)=O)([F:24])[F:23])(=O)=O>[Cu]I.C(#N)C>[CH2:6]([CH:6]1[C:5]2[C:9](=[CH:10][C:2]([Br:1])=[CH:3][CH:4]=2)[C:8](=[O:11])[C:7]21[CH2:16][CH2:15][CH:14]([O:17][CH:22]([F:24])[F:23])[CH2:13][CH2:12]2)[C:5]1[CH:9]=[CH:10][CH:2]=[CH:3][CH:4]=1

Participants

5

Reactant 2

HCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 581970336'-Bromo-4-hydroxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one

Product 1

HCID 67043563benzyl 6'-bromo-4-(difluoromethoxy)spiro[cyclohexane-1,2'-inden]-1'(3'H)-oneYield 63.6%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

In a 25 mL round bottom flask was placed 6′-bromo-4-hydroxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (368 mg, 1.252 mmol) and it was azeotroped twice with acetonitrile (2 mL/each). CuI (24 mg, 0.126 mmol) was added followed by acetonitrile (2.5 mL). This solution was purged under a stream of N2 for 30 seconds. The solution was heated to 60° C. under a nitrogen atmosphere. After being 5 minutes at 60° C., FSO2CF2CO2H (136 mL, 1.316 mmol) was added dropwise. After 1 hour, the reaction was quenched with H2O (10 mL) and diluted with diethyl ether (10 mL). The phases were separated and the aqueous phase was back-extracted with diethyl ether (5 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated under reduce pressure. The crude material was purified by flash chromatography (ISCO, 40 g SiO2 cartridge, ethyl acetate/hexanes as the eluents). The corresponding fractions were combined and concentrated under reduce pressure yielding benzyl 6′-bromo-4-(difluoromethoxy)spiro[cyclohexane-1,2′-inden]-1′(3′H)-one (137 mg, 0.398 mmol, 32% yield). M+H=344.9, 1H NMR (CDCl3, 400 MHz) δ 7.86 (d, J=1.2 Hz, 1H), 7.69 (dd, J=8.0, 1.6 Hz, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.26 (t, J=75.2 Hz, 1H), 4.20 (m, 1H), 2.98 (s, 2H), 2.14 (m, 2H), 1.80 (m, 2H), 1.65-1.52 (m, 4H).

Workup

  1. customIn a 25 mL round bottom flask was placed
  2. customThis solution was purged under a stream of N2 for 30 seconds
  3. waitAfter 1 hour
  4. customthe reaction was quenched with H2O (10 mL)
  5. additiondiluted with diethyl ether (10 mL)
  6. customThe phases were separated
  7. extractionthe aqueous phase was back-extracted with diethyl ether (5 mL)
  8. dry with materialThe combined organic phases were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by flash chromatography (ISCO, 40 g SiO2 cartridge, ethyl acetate/hexanes as the eluents)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-0cd20f9ea426485390e83ee0054e60ef
Source dataset
uspto-grants-2015_12
Patent number
US09212153B2

Reaction notes

Loading…