Chloride → HCID 25142740, compound

HRID 1987804Notes

Reaction equation

HRID 1987804 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH:16]([O:17][CH2:18][CH3:19])[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+].[Cl-]>CCO.O.ClCCl.CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C@:6]3([C@@H:12]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=4)[CH2:13][C:14](=[O:20])[NH:28][CH2:15][C@H:16]3[O:17][CH2:18][CH3:19])[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C@@:6]3([C@H:12]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=4)[CH2:13][C:14](=[O:20])[NH:28][CH2:15][C@@H:16]3[O:17][CH2:18][CH3:19])[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C@:6]3([C@@H:16]([O:17][CH2:18][CH3:19])[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.[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C@@:6]3([C@H:16]([O:17][CH2:18][CH3:19])[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

11

Reactant 4

HCID 312ChlorideHCID 14798Sodium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 68905349HCID 68905349, compound

Product 4

HCID 25142740HCID 25142740, compoundHCID 25142741HCID 25142741, compoundHCID 57724948HCID 57724948, compoundHCID 57724968HCID 57724968, compound

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-ethoxy-spiro[cyclohexane-1,3′-[3H]indole]-2′,4(1′H)-dione (150.0 mg, 0.34 mmole) was reacted with NH2OH—HCl (119.5 mg, 1.72 mmol), NaOH (68.8 mg, 1.72 mmole) in EtOH-water (3/2, 10 mL) at refluxing for 2 hrs, followed by reacting with p-oluenesulfonyl chloride (133.1 mg, 0.70 mmol) in dichloromethane (10 mL) at room temperature for 2 hrs, 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 (3S,4S,5R)-6′-chloro-5-(3-chlorophenyl)-3-ethoxy-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (10.2 mg), (3R,4R,5S)-6′-chloro-5-(3-chlorophenyl)-3-ethoxyl-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (10.8 mg), (3S,4R,5S)-6′-chloro-3-(3-chlorophenyl)-5-ethoxy-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (3.8 mg) and (3R,4S,5R)-6′-chloro-3-(3-chlorophenyl)-5-ethoxy-1,1′,2,2′,3,5,6,7-octahydrospiro[4H-azepine-4,3′-[3H]-indole]-2′,7-dione (3.6 mg).

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-453e3da06a314826b3b8bf7f905b1a0b
Source dataset
uspto-grants-2009_06
Patent number
US07553833B2

Reaction notes

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