Potassium Acetate → 2-Bromo-6-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-fluorobenzaldehyde

HRID 1026511Notes

Reaction equation

HRID 1026511 reaction equation
[CH3:1][C:2]1([CH3:15])[CH2:13][C:12]2[CH:11]=[C:10]3[N:5]([CH2:6][CH2:7][NH:8][C:9]3=[O:14])[C:4]=2[CH2:3]1.[Br:16][C:17]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21](Cl)[C:18]=1[CH:19]=[O:20].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])(=O)C.[K+]>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].O1CCOCC1>[Br:16][C:17]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([N:8]2[CH2:7][CH2:6][N:5]3[C:10](=[CH:11][C:12]4[CH2:13][C:2]([CH3:15])([CH3:1])[CH2:3][C:4]=43)[C:9]2=[O:14])[C:18]=1[CH:19]=[O:20]

Participants

7

Reactant 4

HCID 517044Potassium AcetateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 580442027,7-dimethyl-3,4,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-oneHCID 866837732-Bromo-6-chloro-4-fluorobenzaldehyde

Product 1

HCID 866837722-Bromo-6-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-fluorobenzaldehydeYield 50%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 103e (1.0 g, 4.90 mmol, 1.0 eq.), 2-bromo-6-chloro-4-fluorobenzaldehyde (2.76 g, 9.8 mmol, 2.0 eq.), Pd2(dba)3 (224 mg, 0.24 mmol, 0.050 eq.), Xantphos (283 mg, 0.49 mmol, 0.10 eq.), potassium acetate (1.44 g, 14.7 mmol, 3.0 eq.), and 1,4-dioxane (50 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 80° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol to afford 128a as a yellow solid (992 mg, 50%). MS: [M+H]+ 405.1

Workup

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureAfter this time the reaction was cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified on silica-gel column
  8. washeluting with 80:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-8069aae29dd54d7ab4059d820750c763
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Reaction notes

Loading…