HCID 58458732, compound → HCID 178424242, compound

HRID 1966002Notes

Reaction equation

HRID 1966002 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][C:5]2[N:6]3[C:10]([CH2:11][N:12]([CH3:14])[CH2:13][C:4]=2[CH:3]=1)=[N:9][N:8]=[C:7]3[CH:15]1[CH2:20][CH2:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])=[CH:17][CH2:16]1.[H][H]>C(O)(=O)C.[Pt](=O)=O>[Cl:1][C:2]1[CH:29]=[CH:28][C:5]2[N:6]3[C:10]([CH2:11][N:12]([CH3:14])[CH2:13][C:4]=2[CH:3]=1)=[N:9][N:8]=[C:7]3[C@H:15]1[CH2:16][CH2:17][C@@H:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])[CH2:19][CH2:20]1.[Cl:1][C:2]1[CH:29]=[CH:28][C:5]2[N:6]3[C:10]([CH2:11][N:12]([CH3:14])[CH2:13][C:4]=2[CH:3]=1)=[N:9][N:8]=[C:7]3[C@H:15]1[CH2:16][CH2:17][C@H:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])[CH2:19][CH2:20]1.[CH3:14][N:12]1[CH2:11][C:10]2[N:6]([C:7]([C@H:15]3[CH2:16][CH2:17][C@@H:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH3:27])[CH2:19][CH2:20]3)=[N:8][N:9]=2)[C:5]2[CH:28]=[CH:29][CH:2]=[CH:3][C:4]=2[CH2:13]1

Participants

7

Reactant 2

HCID 58458732HCID 58458732, compoundHCID 178418361HCID 178418361, compound

Product 3

HCID 178424242HCID 178424242, compoundHCID 178424243HCID 178424243, compoundHCID 178424244HCID 178424244, compound

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 176Acetic AcidSolvent

Procedure

A solution of (RS)-8-chloro-5-methyl-1-(4-o-tolyl-cyclohex-3-enyl)-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulene (0.10 g, 0.25 mmol) in acetic acid (2.5 ml) was purged with argon. After addition of platinum(IV) oxide (0.017 g, 0.075 mmol) the reaction vessel was filled with hydrogen. The reaction mixture was stirred under an atmosphere of hydrogen (1 bar) at room temperature for 48 h. The catalyst was removed by filtration over Decalite®. The filtrate was partitioned between ethyl acetate and aqueous 2 M sodium carbonate solution. The organic layer was collected. The aqueous layer was extracted with one portion of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated to dryness. Consecutive purification by flash column chromatography over aminopropyl modified silica gel with n-heptane/ethyl acetate as eluent and HPLC using a Chiralpac® AD column with n-heptane/2-propanol as eluent gave cis-8-chloro-5-methyl-1-(4-o-tolyl-cyclohexyl)-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulene as white solid in 20% yield, trans-8-chloro-5-methyl-1-(4-o-tolyl-cyclohexyl)-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulene as white solid in 11% yield and cis-5-methyl-1-(4-o-tolyl-cyclohexyl)-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulene as off-white solid in 8% yield.

Workup

  1. customThe catalyst was removed by filtration over Decalite®
  2. customThe filtrate was partitioned between ethyl acetate and aqueous 2 M sodium carbonate solution
  3. customThe organic layer was collected
  4. extractionThe aqueous layer was extracted with one portion of ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. concentrationconcentrated to dryness
  7. custompurification by flash column chromatography over aminopropyl

Sources & evidence

ORD record
ord-fe354538bb5242199b5864ff5dcb85b0
Source dataset
uspto-grants-2013_04
Patent number
US08420633B2

Reaction notes

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