Aniline → HCID 15868937, compound

HRID 2267982Notes

Reaction equation

HRID 2267982 reaction equation
N1C2C(=CC=C3C=CC=CC3=2)C[CH2:2]1.[C:14]1([N:20]2[C:28]3[C:23](=[C:24]([OH:33])[CH:25]=[C:26]4[CH:32]=[CH:31][CH:30]=[CH:29][C:27]4=3)C(C)(C)C2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[O-]S(C(F)(F)F)(=O)=O.NC1C=CC=CC=1>[Pd]>[NH:20]([C:28]1[C:27]2[C:26](=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:25]=[C:24]([O:33][CH3:2])[CH:23]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 2758875TrifluoromethanesulfonateHCID 9882438HCID 9882438, compoundHCID 16793165HCID 16793165, compound

Product 1

HCID 15868937HCID 15868937, compound

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

A second preferred synthesis method suitable for the synthesis of benzoindoline compounds, e.g., N-phenyl-3,3-dimethyl-4-hydroxy-benzoindoline 9, is also shown in FIG. 1. In this method, the 3-methoxy napthalene-1-triflate 2 is derivatized with a primary amine, e.g., aniline, using a palladium catalyzed triflate coupling reaction to give a secondary amine, e.g., 1-anilino-3-methoxy napthalene 5. The secondary amine 5 is acetylated using an acid chloride, e.g., an haloacetylchloride, to give a disubstituted amide, e.g., 1-amido-3-methoxy napthalene 6. The tertiary amide 6 is cyclized using a Lewis-acid-catalyzed Friedel-Crafts cyclization procedure to give compound 7, e.g., using AlCl3. Compound 7 is than reduced, e.g., using LAH, to give compound 8. Subsequent methoxy group deprotection by a boron tribromide deprotection procedure gives the benzoindoline, e.g., N-phenyl-3,3-dimethyl-4-hydroxy-benzoindoline 9. An example of this synthesis is provided in Example 2 below.

Workup

  1. customA second preferred synthesis method

Sources & evidence

ORD record
ord-00e0c8f7cdca4ea2844f07d9210874bc
Source dataset
uspto-grants-2001_12
Patent number
US06326153B2

Reaction notes

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