4-Toluenesulfonyl chloride → HCID 57724951, compound

HRID 1987796Notes

Reaction equation

HRID 1987796 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH:16]([CH:17]4[CH2:19][CH2:18]4)[CH2:15][C:14](=[O:20])[CH2:13][CH:12]3[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[NH2:28]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]([CH:17]4[CH2:19][CH2:18]4)[CH2:15][C:14](=[O:20])[NH:28][CH2:13][C@@H:12]3[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=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 67213473HCID 67213473, compound

Product 1

HCID 57724951HCID 57724951, compoundYield 14.6%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
90 °C

Procedure

In a manner similar to the method described in example 2 (method B), rac-(1R,2S,6R)-6′-chloro-2-(3-chlorophenyl)-6-cyclopropylspiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione (148.1 mg, 0.37 mmole) was reacted with NH2OH—HCl (128.6 mg, 1.85 mmol), NaOH (74.0 mg, 1.85 mmole) in EtOH-water (3/2, 10 mL) at refluxing for 2 hrs, followed by reacting with p-toluenesulfonyl chloride (141.1 mg, 0.74 mmol) in dichloromethane (1 mL) at room temperature for 30 min, and heating under microwave irradiation at 90° 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-cyclopropyl-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (22.5 mg): HRMS (ES+) m/z Calcd for C22H20Cl2N2O2+H [(M+H)+]: 415.0975, Found: 415.0974; (3R,4S,5S)-6′-chloro-5-(3-chlorophenyl)-3-cyclopropyl-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (25.8 mg): HRMS (ES+) m/z Calcd for C22H20Cl2N2O2+H [(M+H)+]: 415.0975, Found: 415.0974; (3S,4R,5R)-6′-chloro-3-(3-chlorophenyl)-5-cyclopropyl-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (14.1 mg): HRMS (ES+) m/z Calcd for C22H20Cl2N2O2+H [(M+H)+]: 415.0975, Found: 415.0975; and (3S,4R,5R)-6′-chloro-5-(3-chlorophenyl)-3-cyclopropyl-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (15.2 mg): HRMS (ES+) m/z Calcd for C22H20Cl2N2O2+H [(M+H)+]: 415.0975, Found: 415.0975.

Workup

  1. temperatureat refluxing for 2 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-72c4b2c038444552b34f53faa81b723e
Source dataset
uspto-grants-2009_06
Patent number
US07553833B2

Reaction notes

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