1,4-Cyclohexadiene → HCID 59854970, compound

HRID 2375464Notes

Reaction equation

HRID 2375464 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([N:16]([CH3:34])[C@H:17]2[CH2:22][CH2:21][N:20](C(OCC3C=CC=CC=3)=O)[CH2:19][C@H:18]2[F:33])=[O:15])[C@:11]([CH2:41][OH:42])([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:10]=1.C1CC=CCC=1>CCO.[Pd]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([N:16]([C@H:17]2[CH2:22][CH2:21][NH:20][CH2:19][C@H:18]2[F:33])[CH3:34])=[O:15])[C@:11]([CH2:41][OH:42])([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:10]=1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 59854983HCID 59854983, compound

Product 1

HCID 59854970HCID 59854970, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of 405 mg (0.58 mmol) of 10-1 in 4 mL of EtOH was added 1.38 mL (14.6 mmol) of 1,4-cyclohexadiene, 100 mg of 10% palladium on carbon, and then stirred overnight. The reaction was filtered through Celite, concentrated, and the residue was dissolved in 3 mL of CH2Cl2. To this was added 3 mL of trifluoroacetic acid, stirring was maintained for 1 h, and then the mixture was partitioned between EtOAc and saturated aqueous NaHCO3 plus 25 mL of 5% aqueous Na2CO3, the organic phase was washed with NaHCO3 again, H2O, brine, dried over Na2SO4, and concentrated by rotary evaporation. The residue was loaded onto a silica gel column and eluted with EtOAc—20:1:1 EtOH/NH4OH/H2O to provide 10-2 as a white solid. There was an impurity of 5% subsequently removed by reverse phase chromatography with 95:5 to 5:95 H2O/CH3CN (both with 0.1% TFA). The fractions were basified with NaHCO3 to provide pure B-2 as a white solid. Data for 10-2: 1HNMR (500 MHz, CDCl3) δ 7.4-7.2 (m, 5H), 7.1-6.9 (mn, 3H), 6.3 (s, 1H), 5.2 (bs, 1H), 4.9 (m, 1H), 4.8-4.6 (m, 2H), 4.45 (m, 1H), 4.2-4.1 (m, 1H), 4.0 (m, 1H), 3.3-3.2 (mn, 2H), 3.1 (s, 3H), 2.85-2.7 (m, 2H), 2.1 (m, 1H), 1.7 (m, 2H) ppm. HRMS (ES) calc'd M+H for C24H26F3N3O2: 446.2050. Found: 446.2059.

Workup

  1. filtrationThe reaction was filtered through Celite
  2. concentrationconcentrated
  3. dissolutionthe residue was dissolved in 3 mL of CH2Cl2
  4. additionTo this was added 3 mL of trifluoroacetic acid
  5. stirringstirring
  6. temperaturewas maintained for 1 h
  7. customthe mixture was partitioned between EtOAc and saturated aqueous NaHCO3 plus 25 mL of 5% aqueous Na2CO3
  8. washthe organic phase was washed with NaHCO3 again
  9. dry with materialH2O, brine, dried over Na2SO4
  10. concentrationconcentrated by rotary evaporation
  11. washeluted with EtOAc—20:1:1 EtOH/NH4OH/H2O

Sources & evidence

ORD record
ord-f1a15650b4cf41dba54df831b580a630
Source dataset
uspto-grants-2008_12
Patent number
US07465746B2

Reaction notes

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