Pyridine → 4'-[2-(1-acetyl-4-piperidinyloxy)-5-chloro-phenyl]-6-chloro-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504469Notes

Reaction equation

HRID 504469 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:39])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[CH2:14][C:13](=[O:30])[NH:12][CH:11]3[C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[CH3:38])[C:5]2=[CH:4][CH:3]=1.[C:40](Cl)(=[O:42])[CH3:41].N1C=CC=CC=1>C(Cl)Cl>[C:40]([N:27]1[CH2:28][CH2:29][CH:24]([O:23][C:17]2[CH:18]=[CH:19][C:20]([Cl:22])=[CH:21][C:16]=2[CH:15]2[CH2:14][C:13](=[O:30])[NH:12][CH:11]([C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[CH3:38])[C:10]32[C:5]2[C:6](=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[NH:8][C:9]3=[O:39])[CH2:25][CH2:26]1)(=[O:42])[CH3:41]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 749287696-chloro-4'-[5-chloro-2-(4-piperidinyloxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 749287704'-[2-(1-acetyl-4-piperidinyloxy)-5-chloro-phenyl]-6-chloro-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 8.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(4-piperidinyloxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (110 mg, 0.2 mmol), acetyl chloride (0.017 mL, 0.24 mmol) in DCM (5 mL) was added pyridine (23 mg, 0.3 mmol) at r.t. The reaction mixture was stirred for 4 h, then concentrated and partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over MgSO4 and concentrated. The residue was purified with Prep-HPLC to give the title compound as a white solid (Yield: 10 mg).

Workup

  1. concentrationconcentrated
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified with Prep-HPLC

Sources & evidence

ORD record
ord-50b72667acf04db0a5755fc5af5a4d60
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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