Water → 4-(5-(4-(2,5-Bis(4-bromophenyl)pyrrolidin-1-yl)phenyl)pyridin-2-yl)morpholine

HRID 1471032Notes

Reaction equation

HRID 1471032 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH:10]([C:13]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=3)[N:9]2[C:20]2[CH:25]=[CH:24][C:23](I)=[CH:22][CH:21]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[CH:37][C:38]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[N:39][CH:40]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>C1COCC1.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]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH:10]([C:13]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=3)[N:9]2[C:20]2[CH:25]=[CH:24][C:23]([C:35]3[CH:36]=[CH:37][C:38]([N:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)=[N:39][CH:40]=3)=[CH:22][CH:21]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 27953634-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl)morpholineHCID 672380122,5-Bis(4-bromophenyl)-1-(4-iodophenyl)pyrrolidine

Product 1

HCID 672365524-(5-(4-(2,5-Bis(4-bromophenyl)pyrrolidin-1-yl)phenyl)pyridin-2-yl)morpholine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The product from Example 185A (0.1 g, 0.171 mmol), 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine (0.050 g, 0.171 mmol), potassium phosphate (0.028 mL, 0.343 mmol), tris(dibenzylideneacetone)dipalladium(0) (1.570 mg, 1.715 μmol) and 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamante (1.504 mg, 5.14 μmol) were combined in THF (1.2 mL)/water (0.4 mL). The mixture was sparged with nitrogen for 15 minutes diluted into EtOAc, washed with 1M sodium bicarbonate, brine, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography on an Isco 12 g silica cartridge eluting with 20-70% EtOAc in hexane gave the title compound as a cream colored powder (91 mg, 86%). %). MS (ESI) m/z 620 (M+H)+.

Workup

  1. customThe mixture was sparged with nitrogen for 15 minutes
  2. additiondiluted into EtOAc
  3. washwashed with 1M sodium bicarbonate, brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography on an Isco 12 g silica cartridge
  8. washeluting with 20-70% EtOAc in hexane

Sources & evidence

ORD record
ord-ed3b2b5379a14cc0927cd019b52dd87c
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

Loading…