Cesium carbonate → HCID 86629690, compound

HRID 2041558Notes

Reaction equation

HRID 2041558 reaction equation
Cl.[CH:2]1([CH2:8][C:9]2[CH:16]=[CH:15][C:12]([CH2:13][NH2:14])=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[Cl:17][C:18]1[CH:34]=[CH:33][C:21]2[CH2:22][CH2:23][N:24]([C:27](=[O:32])[C:28]([F:31])([F:30])[F:29])[CH2:25][CH2:26][C:20]=2[C:19]=1OS(C(F)(F)F)(=O)=O.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+]>CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[Cl:17][C:18]1[CH:34]=[CH:33][C:21]2[CH2:22][CH2:23][N:24]([C:27](=[O:32])[C:28]([F:29])([F:31])[F:30])[CH2:25][CH2:26][C:20]=2[C:19]=1[NH:14][CH2:13][C:12]1[CH:11]=[CH:10][C:9]([CH2:8][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]2)=[CH:16][CH:15]=1

Participants

8

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 66707184HCID 66707184, compound

Product 1

HCID 86629690HCID 86629690, compoundYield 63.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Under a nitrogen atmosphere, add 4-cyclohexylmethyl-benzylamine hydrochloride (352 mg, 1.47 mmol), 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (500 mg, 1.17 mmol), palladium(II) acetate (52.7 mg, 0.235 mmol), BINAP (293 mg, 0.47 mmol) and cesium carbonate (1.53 g, 4.7 mmol) to toluene (20 mL). Heat the mixture at 90° C. for 12h. Cool the mixture to room temperature and dilute with EtOAc (25 mL). Filter the solids through cellulose (20g) and concentrate the filtrate in vacuo. Purify the crude mixture by chromatography on silica gel (45g RediSep column) eluting with hexane/EtOAc (1:0 to 4:1 gradient over 1 h; 80 mL/min) to provide 7-chloro-6-(4-cyclohexylmethyl-benzylamino)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a colorless oil (354 mg, 63%). MS (APCI) m/z: 479 (M+H)+.

Workup

  1. temperatureCool the mixture to room temperature
  2. filtrationFilter the solids through cellulose (20g)
  3. concentrationconcentrate the filtrate in vacuo
  4. customPurify the crude mixture by chromatography on silica gel (45g RediSep column)
  5. washeluting with hexane/EtOAc (1:0 to 4:1 gradient over 1 h; 80 mL/min)

Sources & evidence

ORD record
ord-247a439c68cd4c9fac8b793916d5676b
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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