Cesium carbonate → HCID 66980987, compound

HRID 2279248Notes

Reaction equation

HRID 2279248 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[C:3]=1[CH3:14].[C:15]([O:34][CH2:35][C@@H:36]1[NH:40][C:39](=[O:41])[CH2:38][CH2:37]1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C([O-])([O-])=O.[Cs+].[Cs+].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>O1CCOCC1.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]>[CH3:14][C:3]1[C:4]([C:10]([F:13])([F:12])[F:11])=[C:5]([CH:8]=[CH:9][C:2]=1[N:40]1[C@@H:36]([CH2:35][O:34][C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:37][CH2:38][C:39]1=[O:41])[C:6]#[N:7]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 135442282-[(Triphenylmethoxy)methyl]-3,4-dihydro-2H-pyrrol-5-olHCID 66980994HCID 66980994, compound

Product 1

HCID 66980987HCID 66980987, compoundYield 31.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

The bromo-compound 3f (0.5 g, 1.89 mmol) was dissolved in 1,4-dioxane (10 mL) and (R)-5-((trityloxy)methyl)pyrrolidin-2-one (3g) (0.54 g, 1.51 mmol) was added followed by Cs2CO3 (1.2 g, 3.78 mmol) at room temperature. The reaction mixture was degassed with Argon gas for 30 min, Pd2(dba)3 (0.17 g, 0.18 mmol) and Xanthphos (0.21 g, 0.37 mmol) were added and heated to 80° C. for 12 h. After completion of reaction (by TLC), the reaction mixture was diluted with water (20 mL), filtered through celite bed and the filtrate was washed with water (2×20 mL). The organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure to give the crude compound which was purified by column chromatography to afford (R)-3-methyl-4-(2-oxo-5-((trityloxy)methyl)pyrrolidin-1-yl)-2-(trifluoromethyl)benzonitrile (3h) (0.26 g, 26%) as a brown solid.

Workup

  1. customThe reaction mixture was degassed with Argon gas for 30 min
  2. customAfter completion of reaction (by TLC)
  3. filtrationfiltered through celite bed
  4. washthe filtrate was washed with water (2×20 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude compound which
  9. customwas purified by column chromatography

Sources & evidence

ORD record
ord-5956244ded19401999e62ec626d3c8c1
Source dataset
uspto-grants-2015_09
Patent number
US09133182B2

Reaction notes

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