Dimethyl Sulfoxide → HCID 59822286, compound

HRID 1670513Notes

Reaction equation

HRID 1670513 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(N(CC)CC)C.CS(C)=O.[C]=O.[CH3:40][CH2:41][O:42][C:43](C)=[O:44]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(O)C>[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[C:43]([O:42][CH2:41][CH3:40])=[O:44]

Participants

10

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 178418416HCID 178418416, compound

Product 1

HCID 59822286HCID 59822286, compoundYield 82%

Reagents, catalysts & solvents 4

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Add 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (213 g, 500 mmol), triethylamine (118 g, 1150 mmol), palladium(II) acetate (5.6 g, 25 mmol) and 1,3-bis(diphenylphosphino)propane (6.4 g, 15 mmol) to anhydrous DMSO (2.1 L) and ethanol (640 mL) in a 1 gallon autoclave. Inert the autoclave with nitrogen then charge the mixture with carbon monoxide at 50 psi and heat at 100° C. for 2 h (monitor reaction by HPLC). Cool the autoclave to room temperature and add the dark reaction mixture to a flask containing water (3.2 L) and EtOAc (3.2 L). Collect the organic layer and back extract the aqueous layer with EtOAc (2.1 L). Wash the combined organic extracts with water (2.1 L). Concentrate the organic layer in vacuo to a dark oil. Purify the crude mixture by chromatography on silica gel eluting with heptane/EtOAc (5:1) to give the desired intermediate as a pale green oil (144 g, 82%).

Workup

  1. custom(monitor reaction by HPLC)
  2. temperatureCool the autoclave to room temperature
  3. additionadd
  4. customthe dark reaction mixture to a flask
  5. customCollect the organic layer
  6. extractionback extract the aqueous layer with EtOAc (2.1 L)
  7. washWash the combined organic extracts with water (2.1 L)
  8. concentrationConcentrate the organic layer in vacuo to a dark oil
  9. customPurify the crude mixture by chromatography on silica gel eluting with heptane/EtOAc (5:1)

Sources & evidence

ORD record
ord-d27d30a1c14e48d98daa99a23ea468d3
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

Loading…