Oxalyl chloride → HCID 11466973, compound

HRID 968681Notes

Reaction equation

HRID 968681 reaction equation
[C:1]([C@:3]([CH3:26])([C@H:7]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:24][CH3:25])[C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1)[C:4](O)=[O:5])#[N:2].C(Cl)(=O)C(Cl)=O.[CH3:33][O:34][C:35]1[CH:36]=[C:37]([N:43]2[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH:38]=[C:39]([O:41][CH3:42])[CH:40]=1>C1COCC1.CN(C=O)C.CN(C1C=CN=CC=1)C.ClCCl>[CH3:33][O:34][C:35]1[CH:36]=[C:37]([N:43]2[CH2:44][CH2:45][N:46]([C:4](=[O:5])[C@:3]([C@H:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])[C:8]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH:11]=[CH:10][CH:9]=3)([CH3:26])[C:1]#[N:2])[CH2:47][CH2:48]2)[CH:38]=[C:39]([O:41][CH3:42])[CH:40]=1

Participants

8

Reactant 3

HCID 65578Oxalyl chlorideHCID 27362051-(3,5-Dimethoxyphenyl)piperazineHCID 69132851HCID 69132851, compound

Product 1

HCID 11466973HCID 11466973, compoundYield 71.4%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (S,S)2-cyano-3-(2-methoxy-phenyl)-2-methyl-3-naphthalen-1-yl-propionic acid (0.45 g, 1.30 mmol) in THF (150 mL) is treated with DMF (2 drops). Oxalyl chloride (0.16 mL, 1.84 mmol) is added dropwise in order to control gas evolution; when the gas evolution stopped the solution is heated to reflux for 5 minutes. The solution is cooled, the THF is evaporated in vacuo and the solid is dissolved in dry toluene (15 mL) and evaporated to a solid. This procedure is repeated twice. The acid chloride is dissolved in dichloromethane (10 mL) this is added to a solution of 1-(3,5-dimethoxy-phenyl)-piperazine (305 mg, 1.36 mmol) and a crystal of DMAP in dichloromethane (15 mL). This is followed by the dropwise addition of TEA (0.6 mL, 4.27 mmol). The reaction is stirred overnight. The reaction mixture is diluted with dichloromethane (50 mL), washed with aqueous HCl (10 mL 0.5 N) then saturated NaHCO3 (10 mL) and brine (10 mL). The sample is dried over NaSO4, filtered and concentrated in vacuo. Chromatography on silica gel using 30% ethyl acetate/hexanes provided 510 mg the title compound as a white solid. Recrystallization from ethyl acetate/hexanes yielded colorless needles. mp 186-188° C.; [α]D25=−153.91° (1%, CHCl3);

Workup

  1. temperatureis heated
  2. temperatureto reflux for 5 minutes
  3. temperatureThe solution is cooled
  4. customthe THF is evaporated in vacuo
  5. dissolutionthe solid is dissolved in dry toluene (15 mL)
  6. customevaporated to a solid
  7. dissolutionThe acid chloride is dissolved in dichloromethane (10 mL)
  8. washwashed with aqueous HCl (10 mL 0.5 N)
  9. dry with materialThe sample is dried over NaSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f6cb9839c5a64c42bcf990e5b0e93f6c
Source dataset
uspto-grants-2007_12
Patent number
US07304073B2

Reaction notes

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