Oxalic Acid → HCID 69802998, compound

HRID 2179943Notes

Reaction equation

HRID 2179943 reaction equation
Cl[CH2:2][CH2:3][C@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5].[H-].[Na+].[Cl:14][C:15]1[C:22]([F:23])=[CH:21][C:18]([C:19]#[N:20])=[C:17](F)[CH:16]=1.[I-].[Na+].C(N(CC)CC)C.[CH:34]1([NH2:37])[CH2:36][CH2:35]1.[C:38]([OH:43])(=[O:42])[C:39]([OH:41])=[O:40]>O1CCCC1.CCOCC.O.CO>[C:38]([OH:43])(=[O:42])[C:39]([OH:41])=[O:40].[Cl:14][C:15]1[C:22]([F:23])=[CH:21][C:18]([C:19]#[N:20])=[C:17]([O:5][C@@H:4]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:3][CH2:2][NH:37][CH:34]2[CH2:36][CH2:35]2)[CH:16]=1

Participants

12

Reactant 7

HCID 971Oxalic AcidHCID 5238Sodium IodideHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 69828CyclopropylamineHCID 642409(1R)-3-chloro-1-phenylpropan-1-olHCID 112753024-Chloro-2,5-difluorobenzonitrile

Product 1

HCID 69802998HCID 69802998, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

(R)-α-(2-Chloroethyl)benzenemethanol (341 mg, 2 mmol) was dissolved in tetrahydrofuran (10 ml) and treated with sodium hydride as a 60% suspension in mineral oil (480 mg, 3 mmol) followed after 10 minutes by 4-chloro-2,5-difluorobenzonitrile (347 mg, 2 mmol). The mixture was stirred at room temperature for 18 h before being treated with methanol (1 ml) and then water (10 ml). The tetrahydrofuran was then removed via heating the vessel to 80° C. and applying a nitrogen stream. Once the tetrahydrofuran was evaporated the residue was extracted into dichloromethane, dried over magnesium sulphate and concentrated in vacuo. The resultant material was re-dissolved into dimethylformamide (8 ml) and treated with sodium iodide (305 mg, 2.03 mmol), triethylamine (565 μl, 4.06 mmol) and cyclopropylamine (114 mg, 2 mmol) before being heated to 60° C. for 5 days. The mixture was filtered and purified via RPHPLC on the crude reaction material. The purified compound was then treated with 50% saturated oxalic acid in ether to produce 74 mg of a white powder that was collected via filtration.

Workup

  1. customThe tetrahydrofuran was then removed
  2. temperaturevia heating the vessel to 80° C.
  3. customOnce the tetrahydrofuran was evaporated the residue
  4. extractionwas extracted into dichloromethane
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resultant material was re-dissolved into dimethylformamide (8 ml)
  8. temperaturebefore being heated to 60° C. for 5 days
  9. filtrationThe mixture was filtered
  10. custompurified via RPHPLC on the crude
  11. customreaction material

Sources & evidence

ORD record
ord-f219d655eeda40b9a6a9db0f08215e19
Source dataset
uspto-grants-2005_05
Patent number
US06887871B2

Reaction notes

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