Tributyl(prop-1-yn-1-yl)stannane → HCID 76568031, compound

HRID 1728145Notes

Reaction equation

HRID 1728145 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:35])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28](I)[CH:27]=[CH:26][C:25]=3[O:31][CH2:32][CH2:33][OH:34])[C:5]2=[CH:4][CH:3]=1.[CH2:36]([Sn](CCCC)(CCCC)C#CC)[CH2:37][CH2:38]C>O1CCOCC1.[Cu]I.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].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:35])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28]([C:36]#[C:37][CH3:38])[CH:27]=[CH:26][C:25]=3[O:31][CH2:32][CH2:33][OH:34])[C:5]2=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 2733165Tributyl(prop-1-yn-1-yl)stannaneHCID 76567917HCID 76567917, compound

Product 1

HCID 76568031HCID 76568031, compoundYield 99.2%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-[5-iodo-2-(2-hydroxy-ethoxy)-phenyl]spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (0.2 g, 0.32 mmol) prepared in Example 190c in dioxane (10 mL) was added CuI (5 mg, 0.026 mmol) (Aldrich). The mixture was degassed under nitrogen for 5 min, then tris(dibenzylideneacetone)dipalladium(0) (23 mg, 0.026 mmol, Strem), tri-phenylphosphine (6.7 mg, 0.026 mmol), and tributyl(1-propynyl)tin (1.1 g, 3.2 mmol, Aldrich) were added sequentially. The reaction mixture was heated at 80° C. under nitrogen for 1 h. After cooled to room temperature, the reaction mixture was filtered through a short pad of celite. The filtrate was partitioned between saturated water and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by chromatography to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-[2-(2-hydroxy-ethoxy)-5-(1-propynyl)-phenyl]spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a yellow solid (Yield 0.17 g, 99%).

Workup

  1. customThe mixture was degassed under nitrogen for 5 min
  2. temperatureAfter cooled to room temperature
  3. filtrationthe reaction mixture was filtered through a short pad of celite
  4. customThe filtrate was partitioned between saturated water and ethyl acetate
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography

Sources & evidence

ORD record
ord-b33ed5c68a87407e9724e6be587d9620
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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