Water → HCID 67100256, compound

HRID 1868804Notes

Reaction equation

HRID 1868804 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](Cl)[CH:10]=2)[C:5]2([CH2:16][CH2:15][CH2:14][CH2:13]2)[C:4](=[O:17])[C:3]=1[C:18]([NH:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:19].[C:29]1(B(O)O)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C([O-])([O-])=O.[K+].[K+].O.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:10]=2)[C:5]2([CH2:16][CH2:15][CH2:14][CH2:13]2)[C:4](=[O:17])[C:3]=1[C:18]([NH:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:19]

Participants

9

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67099598HCID 67099598, compound

Product 1

HCID 67100256HCID 67100256, compoundYield 41.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To 1,1-dimethylethyl N-((4′-hydroxy-2′-oxo-6′-chloro-spiro[cyclopentane-1,1′-naphthalen]-3′-yl)carbonyl)glycinate (250 mg, 616 μmol, Example 25A-B) and phenylboronic acid (113 mg, 924 μmol) were added 1,4-dioxane (3080 μL) and K2CO3 in water (924 μL, 1848 μmol). The reaction was then flushed with nitrogen for 10 minutes. Pd2(dba)3 (56.4 mg, 61.6 μmol) and X-Phos (58.7 mg, 123 μmol) were then added, and the reaction mixture was stirred at 110° C. for 6 hours. The reaction mixture was diluted with 75 mL of EtOAc, added to a separatory funnel, partitioned with NaHCO3 (saturated, aqueous), washed 2 times with 50 mL of NaHCO3 (saturated, aqueous), separated, dried over Na2SO4, and concentrated in vacuo to give the title compound (115 mg) as an oil after preparatory LC. MS (m/z)=392(M+H-tBu)+.

Workup

  1. customThe reaction was then flushed with nitrogen for 10 minutes
  2. additionadded to a separatory funnel
  3. custompartitioned with NaHCO3 (saturated, aqueous)
  4. washwashed 2 times with 50 mL of NaHCO3 (saturated, aqueous)
  5. customseparated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7dc8eb59da0f44c496f237ee6b08ce20
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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