Oxalyl chloride → HCID 58573299, compound

HRID 932248Notes

Reaction equation

HRID 932248 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:27][CH3:28])[CH2:22][S:23](O)(=[O:25])=[O:24])[C:11](=[O:29])[C@:10]([CH2:31][C:32]([O:34][CH3:35])=[O:33])([CH3:30])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[O:42]1[CH2:45][CH:44]([NH2:46])[CH2:43]1.C(N(CC)C(C)C)(C)C>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:27][CH3:28])[CH2:22][S:23](=[O:24])(=[O:25])[NH:46][CH:44]3[CH2:45][O:42][CH2:43]3)[C:11](=[O:29])[C@:10]([CH2:31][C:32]([O:34][CH3:35])=[O:33])([CH3:30])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 98339233-OxetanamineHCID 58573515HCID 58573515, compound

Product 1

HCID 58573299HCID 58573299, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-(2-methoxy-2-oxoethyl)-3-methyl-2-oxopiperidin-1-yl)butane-1-sulfonic acid (189.8 mg, 0.35 mmol; Example 372, Step B) in dichloromethane (5.0 mL) was added oxalyl chloride (0.061 mL, 0.70 mmol), followed by DMF (2 drops). The reaction was stirred at room temperature for 3.5 hours, then concentrated in vacuo. The sulfonyl chloride intermediate was dissolved in dichloromethane (5.0 mL), then treated with 3-oxetanamine (50.0 mg, 0.684 mmol; Pharmablock R & D Co. Ltd., Nanjing, China) and N,N-diisopropylethylamine (0.122 mL, 0.699 mmol). After stirring at room temperature for 16 hours, the reaction was quenched with methanol (2.0 mL), then concentrated in vacuo. Purification of the residue by chromatography on silica gel (4 g SiO2, 0%-50% EtOAc in hexanes) provided the title compound as a colorless oil.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe sulfonyl chloride intermediate was dissolved in dichloromethane (5.0 mL)
  3. stirringAfter stirring at room temperature for 16 hours
  4. customthe reaction was quenched with methanol (2.0 mL)
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by chromatography on silica gel (4 g SiO2, 0%-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-87f67dd680e1445abd3dbdb112a9a741
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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