4-Bromobutyryl chloride → 8-[Dihydro-furan-(2z)-ylidenemethanesulfonyl]-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 2194191Notes

Reaction equation

HRID 2194191 reaction equation
[CH3:1][S:2]([N:5]1[CH2:26][CH2:25][C:8]2([C:12](=[O:13])[N:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].[Li]CCCC.Br[CH2:33][CH2:34][CH2:35][C:36](Cl)=[O:37]>C1COCC1>[O:37]1[CH2:36][CH2:35][CH2:34]/[C:33]/1=[CH:1]/[S:2]([N:5]1[CH2:6][CH2:7][C:8]2([C:12](=[O:13])[N:11]([C:14]3[CH:15]=[CH:16][C:17]([O:20][C:21]([F:23])([F:22])[F:24])=[CH:18][CH:19]=3)[CH2:10][CH2:9]2)[CH2:25][CH2:26]1)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 702254-Bromobutyryl chlorideHCID 595779498-Methanesulfonyl-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-oneHCID 178418339Butyllithium2×

Product 1

HCID 595779038-[Dihydro-furan-(2z)-ylidenemethanesulfonyl]-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-oneYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 8-methanesulfonyl-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (described in example 208, step A) (50 mg, 13 mmol) in THF (3 mL) at −78° C. was added nBuLi (1.6M solution in heptane, 80 uL, 13 mmol), and the reaction mixture was stirred at −78° C. for 10 mins. Then a solution of 4-bromo-butyryl chloride (15 uL 0.13 mmol) in THF (1 mL) was added and the reaction mixture was stirred for a further 30 mins at −78° C. and then another 2 equivalents of nBuLi were added and the reaction mixture was warmed to room temperature. The reaction was quenched with water and extracted with ethyl acetate. The organic phases were combined, dried (Na2SO4), filtered and concentrated in vacuo to give a crude residue was purified by flash column chromatography (4:1 AcOEt/heptane) to yield 8-[dihydro-furan-(2Z)-ylidenemethanesulfonyl]-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (15 mg, 26%) as a white solid. MS (ESI): 461.4 (MH+).

Workup

  1. stirringthe reaction mixture was stirred for a further 30 mins at −78° C.
  2. temperaturethe reaction mixture was warmed to room temperature
  3. customThe reaction was quenched with water
  4. extractionextracted with ethyl acetate
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a crude residue
  9. customwas purified by flash column chromatography (4:1 AcOEt/heptane)

Sources & evidence

ORD record
ord-15c325469c744adbaa5b5ffa936ec0e6
Source dataset
uspto-grants-2012_12
Patent number
US08329904B2

Reaction notes

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