1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 59371579, compound

HRID 2095396Notes

Reaction equation

HRID 2095396 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][NH:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:18]1[CH:19]=[N:20][CH:21]=[C:22]([O:24][CH2:25][C@@H:26]2[CH2:30][CH2:29][CH2:28][N:27]2[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:23]=1.CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:8][CH2:9][CH2:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][N:14]([C:18]2[CH:19]=[N:20][CH:21]=[C:22]([O:24][CH2:25][C@@H:26]3[CH2:30][CH2:29][CH2:28][N:27]3[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:23]=2)[CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 15480235(S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl esterHCID 23676156Sodium t-butoxideHCID 59371324HCID 59371324, compound

Product 1

HCID 59371579HCID 59371579, compoundYield 99.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
99 °C

Procedure

To a solution of 3(R)-[3-(benzyloxy)propyl]pyrrolidine (350 mg, 1.60 mmol) and 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (627 mg, 1.76 mmol, 1.1 equiv.) in 10 mL of anhydrous toluene were added successively at room temperature sodium tert-butoxide (307 mg, 3.20 mmol, 2.0 equiv.), tris(dibenzylideneacetone)dipalladium(0) (99 mg, 0.10 mmol, 0.06 equiv.) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 111 mg, 0.19 mmol, 0.12 equiv.). The mixture was degassed and purged with nitrogen (3 cycles) and then heated to 98-100° C. After 4 h, the mixture was cooled to room temperature, diluted with EtOAc, and washed with brine. After drying over Na2SO4, the solvent was evaporated, and the residue was purified by CC (SiO2, CH2Cl2/EtOAc 8:1 to 3:1) to obtain the product (791 mg, 63%) as a light yellow oil. LC-MS (ESI) m/z 496 (M+H+).

Workup

  1. customThe mixture was degassed
  2. custompurged with nitrogen (3 cycles)
  3. temperaturethe mixture was cooled to room temperature
  4. additiondiluted with EtOAc
  5. washwashed with brine
  6. dry with materialAfter drying over Na2SO4
  7. customthe solvent was evaporated
  8. customthe residue was purified by CC (SiO2, CH2Cl2/EtOAc 8:1 to 3:1)

Sources & evidence

ORD record
ord-0bbf0428120b408c9582d9f3b14813c9
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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