Phosphorus oxychloride → HCID 86641069, compound

HRID 383953Notes

Reaction equation

HRID 383953 reaction equation
[C:1]([C:4]1[S:5][C:6]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:7]([NH:9][C:10](=[O:21])[O:11][CH2:12][C:13]23[CH2:20][CH2:19][N:16]([CH2:17][CH2:18]2)[CH2:15][CH2:14]3)[N:8]=1)(=O)[NH2:2].P(Cl)(Cl)([Cl:30])=O.C([O-])(O)=O.[Na+].Cl.CCOC(C)=O>CN(C=O)C.CCOC(C)=O>[ClH:30].[C:1]([C:4]1[S:5][C:6]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[C:7]([NH:9][C:10](=[O:21])[O:11][CH2:12][C:13]23[CH2:14][CH2:15][N:16]([CH2:17][CH2:18]2)[CH2:19][CH2:20]3)[N:8]=1)#[N:2]

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 21866389Hydrogen chloride-ethyl acetateHCID 59291311HCID 59291311, compound

Product 1

HCID 86641069HCID 86641069, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

To a solution of 1-azabicyclo[2.2.2]oct-4-ylmethyl (2-carbamoyl-5-phenyl-1,3 thiazol-4-yl)carbamate (100 mg) in DMF (5 mL) was added phosphorous oxychloride (48 μL) at 0° C., followed by stirring for 1 hour. To the reaction mixture was added EtOAc, followed by dilution, addition of an aqueous NaHCO3 solution, and extraction with EtOAc. The organic layer was washed with water and brine in this order, then dried, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3:MeOH:28% aqueous ammonia=9:1:0.1), and the brown oily substance obtained was dissolved in EtOAc, followed by addition of 4 M HCl/EtOAc and stirring. The mixture was concentrated under reduced pressure, EtOAc was added thereto, and the solid precipitated was collected by filtration to obtain 1-azabicyclo[2.2.2]oct-4-ylmethyl (2-cyano-5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride (33 mg) as a pale brown solid.

Workup

  1. washThe organic layer was washed with water and brine in this order
  2. customdried
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (CHCl3:MeOH:28% aqueous ammonia=9:1:0.1)
  5. customthe brown oily substance obtained
  6. stirringstirring
  7. concentrationThe mixture was concentrated under reduced pressure, EtOAc
  8. additionwas added
  9. customthe solid precipitated
  10. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-2e7ac74c4ce54fc7b91975738c9b5d05
Source dataset
uspto-grants-2013_02
Patent number
US08367696B2

Reaction notes

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