Cesium carbonate → HCID 86624181, compound

HRID 1191140Notes

Reaction equation

HRID 1191140 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.[CH3:27][C:28]([CH3:43])([CH3:42])[CH2:29][S:30]([CH2:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][CH:35]=1)(=[O:32])=[O:31].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+]>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]>[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:14])([F:13])[F:15])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:39][CH2:38][C:37]1[CH:36]=[CH:35][C:34]([CH2:33][S:30]([CH2:29][C:28]([CH3:43])([CH3:42])[CH3:27])(=[O:32])=[O:31])=[CH:41][CH:40]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 58495491HCID 58495491, compound

Product 1

HCID 86624181HCID 86624181, compoundYield 77.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Use a method similar to the General Procedure 1-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (639 mg, 1.50 mmol) with 4-(2,2-dimethyl-propanesulfonylmethyl)-benzylamine (479 mg, 1.88 mmol), using tris(dibenzylideneacetone)dipalladium(0) (137 mg, 0.15 mmol), BINAP (187 mg, 0.3 mmol) and cesium carbonate (977 mg, 3 mmol) in toluene (20 mL). Heat the mixture at 90° C. overnight. Cool the mixture to room temperature and purify by chromatography on silica gel (80 g) eluting with hexane/EtOAc (1:0 to 4:1 gradient over 15 min; 50 mL/min) to give 7-chloro-6-[4-(2,2-dimethyl-propanesulfonyl-methyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (615 mg, 77%). MS (APCI+) m/z: 531 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. custompurify by chromatography on silica gel (80 g)
  3. washeluting with hexane/EtOAc (1:0 to 4:1 gradient over 15 min; 50 mL/min)

Sources & evidence

ORD record
ord-1ead7dc3ae894fdfba8c660d01d7dd06
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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