1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 59371508, compound

HRID 2095384Notes

Reaction equation

HRID 2095384 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:7]=1.[CH2:22]([O:29][CH2:30][CH2:31][CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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]>[CH2:22]([O:29][CH2:30][CH2:31][CH:32]1[CH2:37][CH2:36][N:35]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([O:8][CH2:9][C@@H:10]3[CH2:14][CH2:13][CH2:12][N:11]3[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:7]=2)[CH2:34][CH2:33]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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 20735327HCID 20735327, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 59371508HCID 59371508, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
99 °C

Procedure

To a mixture of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (72 mg, 0.20 mmol) and 4-[2-(benzyloxy)ethyl]piperidine (44 mg, 0.20 mmol) in anhydrous toluene (2.0 mL) were added successively sodium tert-butoxide (29 mg, 0.30 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (3.7 mg, 4.0 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 6.9 mg, 12 μmol, 0.06 equiv.). The mixture was degassed and purged with Ar (3 cycles), then warmed to 98-100° C. for 4 h. After cooling to room temperature, the mixture was diluted with EtOAc and washed with brine. The solution was dried over Na2SO4 and evaporated, and the residue was purified by CC (SiO2, CH2Cl2/EtOAc 4:1 followed by CH2Cl2/MeOH 10:1) to recover first unreacted 3-bromo-5-[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (14 mg) and subsequently 3-[4-[2-(benzyloxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (67 mg, 85%) as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 7.91-7.78 (m, 2H), 7.37-7.21 (m, 5H), 6.86-6.68 (m, 1H), 4.51 (s, 2H), 4.15 (m, 2H), 3.93-3.82 (m, 1H), 3.67 (m, 2H), 3.54 (t, 2H, J=6.0 Hz), 3.41 (m, 2H), 2.74 (m, 2H), 2.02-1.83 (m, 4H), 1.80-1.62 (m, 2H), 1.61-1.58 (m, 3H), 1.47 (s, 9H), 1.38-1.26 (m, 2H).

Workup

  1. customThe mixture was degassed
  2. custompurged with Ar (3 cycles)
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was diluted with EtOAc
  5. washwashed with brine
  6. dry with materialThe solution was dried over Na2SO4
  7. customevaporated
  8. customthe residue was purified by CC (SiO2, CH2Cl2/EtOAc 4:1 followed by CH2Cl2/MeOH 10:1)
  9. customto recover first unreacted 3-bromo-5-[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (14 mg) and subsequently 3-[4-[2-(benzyloxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (67 mg, 85%) as a pale yellow oil

Sources & evidence

ORD record
ord-a78c96683b384195906443816aa43853
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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