Water → 8-Benzyl-6-hydroxy-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1501795Notes

Reaction equation

HRID 1501795 reaction equation
[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2([C:15](=[O:16])[NH:14][CH2:13][CH2:12]2)[CH:10]([OH:19])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([O-:23])([O-])=[O:21].[K+].[K+].[CH3:26][C:27]1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)O[C:29]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:28]1=2.O>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2([C:15](=[O:16])[N:14]([C:27]3[CH2:26][O:23][C:20](=[O:21])[C:28]=3[CH3:29])[CH2:13][CH2:12]2)[CH:10]([OH:19])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867094868-Benzyl-6-hydroxy-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 867094878-Benzyl-6-hydroxy-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 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a flask charged with 8-benzyl-6-hydroxy-2,8-diazaspiro[4.5]decan-1-one (520 mg, 2.0 mmol) and a stir bar was added palladium acetate (22 mg, 0.10 mmol), K2CO3 (550 mg, 4.00 mmol), Xantphos (120 mg, 0.20 mmol), 4-methyl-5-oxo-2,5-dihydrofuran-3-yltrifluoromethanesulfonate (640 mg, 2.6 mmol), and water (110 mg, 6.0 mmol). The mixture was heated to 60° C. for 2 hours. LC showed complete reaction at that point. The reaction was diluted with EtOAc, washed with water, and the phases separated. The crude solution was dried over Na2SO4, filtered and concentrated to an oil. The oil was loaded onto a silica gel column, and purified by MPLC with Hexane and EtOAc. Two spots were separated with the desired molecular weight in a ratio of about 1 to 7. The more polar spot was the major product. LCMS: m/z 357 (M+H)+.

Workup

  1. customreaction at that point
  2. washwashed with water
  3. customthe phases separated
  4. dry with materialThe crude solution was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. custompurified by MPLC with Hexane and EtOAc
  8. customTwo spots were separated with the desired molecular weight in a ratio of about 1 to 7

Sources & evidence

ORD record
ord-5ceb3e24b1b54cb38f712035ce46e3c6
Source dataset
uspto-grants-2015_12
Patent number
US09206198B2

Reaction notes

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