4-Toluenesulfonyl chloride → HCID 57724939, compound

HRID 1987798Notes

Reaction equation

HRID 1987798 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH:16]([C:17]4[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=4[CH3:24])[CH2:15][C:14](=[O:25])[CH2:13][CH:12]3[C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[NH2:33]O.Cl.[OH-].[Na+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>CCO.O.ClCCl.CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C@@:6]3([C@H:16]([C:17]4[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=4[CH3:24])[CH2:15][C:14](=[O:25])[NH:33][CH2:13][C@@H:12]3[C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 67213809HCID 67213809, compound

Product 1

HCID 57724939HCID 57724939, compoundYield 11.7%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
100 °C

Procedure

In a manner similar to the method described in example 2 (method B), rac-(1S,2S,6R)-6′-chloro-2-(3-chlorophenyl)-6-(5-fluoro-2-methylphenyl)-spiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione (130.0 mg, 0.28 mmole) was reacted with NH2OH—HCl (97.3 mg, 1.40 mmol), NaOH (56.0 mg, 1.40 mmole) in EtOH-water (3/2, 5 mL) at refluxing for 3 hrs, followed by reacting with p-toluenesulfonyl chloride (114.4 mg, 0.60 mmol) in dichloromethane (10 mL) at room temperature for 2 hrs, and heating under microwave irradiation at 100° C. for 20 min. After diluted with AcOEt the mixture was washed with water, dried over Na2SO4 and concentrated. The residue was purified by chiral column chromatography to give (3R,4S,5S)-6′-chloro-3-(3-chlorophenyl)-5-(5-fluoro-2-methylphenyl)-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (15.9 mg): HRMS (ES+) m/z Calcd for C26H21Cl2FN2O2+H [(M+H)+]: 483.1037, Found: 483.1036; (3R,4S,5S)-6′-chloro-5-(3-chlorophenyl)-3-(5-fluoro-2-methylphenyl)-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (11.3 mg): HRMS (ES+) m/z Calcd for C26H21Cl2FN2O2+H [(M+H)+]: 483.1037, Found: 483.1037; (3S,4R,5R)-6′-chloro-5-(3-chlorophenyl)-3-(5-fluoro-2-methylphenyl)-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (8.3 mg): HRMS (ES+) m/z Calcd for C26H21Cl2FN2O2+H [(M+H)+]: 483.1037, Found: 483.1036; (3S,4R,5R)-6′-chloro-3-(3-chlorophenyl)-5-(5-fluoro-2-methylphenyl)-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (12.5 mg): HRMS (ES+) m/z Calcd for C26H21Cl2FN2O2+H [(M+H)+]: 483.1037, Found: 483.1038.

Workup

  1. temperatureat refluxing for 3 hrs
  2. washwas washed with water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by chiral column chromatography

Sources & evidence

ORD record
ord-54ff02a2950846558d5678e80fb36954
Source dataset
uspto-grants-2009_06
Patent number
US07553833B2

Reaction notes

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