Dichloromethane → HCID 74395340, compound

HRID 1987808Notes

Reaction equation

HRID 1987808 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH:16]([O:17][CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:15][C:14](=[O:23])[CH2:13][CH:12]3[C:24]3[CH:29]=C[CH:27]=[C:26](Cl)[CH:25]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[NH2:31]O.Cl.[OH-].[Na+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.Cl[CH2:48][Cl:49]>CCO.O.CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH:16]([O:17][CH2:18][C:19]([CH3:22])([CH3:20])[CH3:21])[CH2:15][C:14](=[O:23])[NH:31][CH2:13][CH:12]3[C:24]3[CH:25]=[CH:26][CH:27]=[C:48]([Cl:49])[CH:29]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 73974-Toluenesulfonyl chlorideHCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 68908424HCID 68908424, compound

Product 1

HCID 74395340HCID 74395340, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 19096565Water ethanolSolvent

Conditions

Temperature
100 °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-(2,2-dimethylpropoxy)-spiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione (167.0 mg, 0.37 mmole) was reacted with NH2OH—HCl (52.0 mg, 0.74 mmol), NaOH (30.0 mg, 0.74 mmole) in EtOH-water (3/2, 7.5 mL) at refluxing for 1 h, followed by reacting with p-toluenesulfonyl chloride (102.0 mg, 0.51 mmol) in dichloromethane (10 mL) at room temperature for 2 hrs, and heating under microwave irradiation at 100° C. for 30 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,5R)-6′-chloro-3-(3-chlorophenyl)-5-(2,2-dimethylpropoxy)-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (11.0 mg): HRMS (ES+) m/z Calcd for C24H26Cl2N2O3+H [(M+H)+]: 461.1393, Found: 461.1393; (3S,4R,5S)-6′-chloro-3-(3-chlorophenyl)-5-(2,2-dimethylpropoxy)-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (7.0 mg): HRMS (ES+) m/z Calcd for C24H26Cl2N2O3+H [(M+H)+]: 461.1393, Found: 461.1393; (3R,4R,5S)-6′-chloro-5-(3-chlorophenyl)-3-(2,2-dimethylpropoxy)-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (7.0 mg): HRMS (ES+) m/z Calcd for C24H26Cl2N2O3+H [(M+H)+]: 461.1393, Found: 461.1394; (3S,4S,5R)-6′-chloro-5-(3-chlorophenyl)-5-(2,2-dimethylpropoxy)-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (7.0 mg): HRMS (ES+) m/z Calcd for C24H26Cl2N2O3+H [(M+H)+]: 461.1393, Found: 461.1394.

Workup

  1. temperatureat refluxing for 1 h
  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-15946b0997d440c2a44bfe365afec54d
Source dataset
uspto-grants-2009_06
Patent number
US07553833B2

Reaction notes

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