1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 59371457, compound

HRID 2095402Notes

Reaction equation

HRID 2095402 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 59371502HCID 59371502, compound

Product 1

HCID 59371457HCID 59371457, compoundYield 99.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
99 °C

Procedure

To a solution of 3(S)-[3-(benzyloxy)propyl]pyrrolidine (330 mg, 1.51 mmol) and 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (592 mg, 1.66 mmol, 1.1 equiv.) in 10 mL of anhydrous toluene were added successively at room temperature sodium tert-butoxide (290 mg, 3.02 mmol, 2.0 equiv.), tris(dibenzylideneacetone)dipalladium(0) (94 mg, 0.09 mmol, 0.06 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 105 mg, 0.18 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 title product (746 mg, 68%) 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-1b4638b0b8024a7ba5dcd24202869005
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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