Cesium carbonate → HCID 86622857, compound

HRID 1013113Notes

Reaction equation

HRID 1013113 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[C:27]([Si:31]([CH3:38])([CH3:37])[O:32][CH:33]1[CH2:36][NH:35][CH2:34]1)([CH3:30])([CH3:29])[CH3:28].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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].C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[N:35]1[CH2:34][CH:33]([O:32][Si:31]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:37])[CH3:38])[CH2:36]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 574386563-((tert-Butyldimethylsilanyl)oxy)azetidineHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 86622857HCID 86622857, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

Use 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (prepared essentially as described in Preparation 1)(979 mg, 2.3 mmol), 3-(tert-butyldimethyl-silanyloxy)-azetidine (880 mg, 4.7 mmol), palladium (II) acetate (51.6 mg, 0.23 mmol), tris(dibenzylideneacetone)dipalladium(0) (211 mg, 0.23 mmol), BINAP (racemic, 215 mg, 0.345 mmol), cesium carbonate (1.1 g, 3.45 mmol), anhydrous toluene (50 mL) and degas and fill with nitrogen (3 times). Seal the system with septum and tighten it with copper wire when necessary. Heat the mixture at 95° C. for 8 h. Dilute with EtOAc, wash with saturated aqueous sodium bicarbonate solution, brine, dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 10:90 EtOAc:hexanes) to give the title compound (763 mg, 72%).

Workup

  1. customdegas
  2. customSeal the system with septum
  3. additionDilute with EtOAc
  4. washwash with saturated aqueous sodium bicarbonate solution, brine
  5. dry with materialdry (sodium sulfate)
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 10:90 EtOAc:hexanes)

Sources & evidence

ORD record
ord-295b673686e14d9ab6f053b1d97092b5
Source dataset
uspto-grants-2011_07
Patent number
US07981882B2

Reaction notes

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