Water → 8-(1-(1-((Tert-butyldimethylsilyl)oxy)-4-methyl-1,3-dihydroisobenzofuran-5-yl)-1-hydroxy-2-methylpropan-2-yl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1848559Notes

Reaction equation

HRID 1848559 reaction equation
[Si:1]([O:8][CH:9]1[C:17]2[C:12](=[C:13]([CH3:34])[C:14]([CH:18]([OH:33])[C:19]([N:22]3[CH2:32][CH2:31][C:25]4([C:29](=[O:30])[NH:28][CH2:27][CH2:26]4)[CH2:24][CH2:23]3)([CH3:21])[CH3:20])=[CH:15][CH:16]=2)[CH2:11][O:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(F)(F)S(O[C:41]1[CH2:42][O:43][C:44](=[O:47])[C:45]=1[CH3:46])(=O)=O.C(=O)([O-])[O-].[K+].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:1]([O:8][CH:9]1[C:17]2[C:12](=[C:13]([CH3:34])[C:14]([CH:18]([OH:33])[C:19]([N:22]3[CH2:23][CH2:24][C:25]4([C:29](=[O:30])[N:28]([C:41]5[CH2:42][O:43][C:44](=[O:47])[C:45]=5[CH3:46])[CH2:27][CH2:26]4)[CH2:31][CH2:32]3)([CH3:21])[CH3:20])=[CH:15][CH:16]=2)[CH2:11][O:10]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 108901884-Methyl-5-oxo-2,5-dihydrofuran-3-yl trifluoromethanesulfonateHCID 867095398-(1-(1-((Tert-butyldimethylsilyl)oxy)-4-methyl-1,3-dihydroisobenzofuran-5-yl)-1-hydroxy-2-methylpropan-2-yl)-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 867095418-(1-(1-((Tert-butyldimethylsilyl)oxy)-4-methyl-1,3-dihydroisobenzofuran-5-yl)-1-hydroxy-2-methylpropan-2-yl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 8-(1-(1-((tert-butyldimethylsilyl)oxy)-4-methyl-1,3-dihydroisobenzofuran-5-yl)-1-hydroxy-2-methylpropan-2-yl)-2,8-diazaspiro[4.5]decan-1-one (1.35 g, 2.76 mmol), 4-methyl-5-oxo-2,5-dihydrofuran-3-yl trifluoromethanesulfonate (I-9) (0.884 g, 3.59 mmol) in toluene (40 mL) was added potassium carbonate (0.764 g, 5.52 mmol), Xantphos (0.320 g, 0.552 mmol), and water (0.149 mL, 8.29 mmol). The mixture was flushed with nitrogen for 20 min before addition of palladium (II) acetate (0.062 g, 0.276 mmol). The resulting mixture was heated at 70° C. overnight. After filtration the filtrate was concentrated and the residue was purified on silica gel column using methanol/methylene chloride as eluting solvents to give the title compound. LC/MS: (M+1−114)+: 471.22.

Workup

  1. filtrationAfter filtration the filtrate
  2. concentrationwas concentrated
  3. customthe residue was purified on silica gel column
  4. washas eluting solvents

Sources & evidence

ORD record
ord-b2c39e94edcb4648a1d59283e6f7620c
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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