Phenylacetyl chloride → HCID 57677633, compound

HRID 492795Notes

Reaction equation

HRID 492795 reaction equation
[C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S-:11][C:12]#[N:13].[K+].C(=O)([O-])O.[Na+].[NH2:20][C:21]1[CH:47]=[CH:46][C:24]([O:25][C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]([N:35]3[CH2:40][CH2:39][CH:38]([N:41]4[CH2:45][CH2:44][CH2:43][CH2:42]4)[CH2:37][CH2:36]3)=[O:34])[CH:27]=2)=[CH:23][CH:22]=1.[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(#N)C.C(O)C.C1(C)C=CC=CC=1>[C:1]1([CH2:7][C:8]([NH:13][C:12](=[S:11])[NH:20][C:21]2[CH:22]=[CH:23][C:24]([O:25][C:26]3[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]([N:35]4[CH2:36][CH2:37][CH:38]([N:41]5[CH2:45][CH2:44][CH2:43][CH2:42]5)[CH2:39][CH2:40]4)=[O:34])[CH:27]=3)=[CH:46][CH:47]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

9

Reactant 5

HCID 7679Phenylacetyl chlorideHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 516872Potassium thiocyanateHCID 516892Sodium BicarbonateHCID 23153457HCID 23153457, compound

Product 1

HCID 57677633HCID 57677633, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolvent2×HCID 6342AcetonitrileSolvent

Procedure

2-Phenylacetyl chloride (0.040 ml) was dissolved in acetonitrile (2.0 ml) under a nitrogen atmosphere, and then potassium thiocyanate (60 mg) was added thereto at 50° C., followed by stirring at the same temperature for 3 hrs. The acetonitrile was evaporated under a reduced pressure to give a residue, to which toluene (2.0 ml) and a saturated aqueous solution of sodium hydrogencarbonate (2.0 ml) were added, followed by stirring for 15 min. The toluene layer (0.7 ml) was added to a solution of 4-(4-aminophenoxy)-2-{[4-(pyrrolidin-1-yl)piperidin-1-yl]carbonylamino}pyridine (27 mg) and (S)-(+)-10-camphorsulfonic acid (32 mg) in ethanol (1.0 ml) at room temperature, followed by stirring for 30 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate). Fractions containing the target compound were concentrated under a reduced pressure to give a residue, which was then dried in vacuum to provide the titled compound (17.2 mg, 44%) as white powder.

Workup

  1. customat 50° C.
  2. customThe acetonitrile was evaporated under a reduced pressure
  3. customto give a residue
  4. stirringby stirring for 15 min
  5. stirringby stirring for 30 min
  6. customThe reaction mixture was partitioned between ethyl acetate
  7. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated
  10. customto give a residue, which
  11. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate)
  12. additionFractions containing the target compound
  13. concentrationwere concentrated under a reduced pressure
  14. customto give a residue, which
  15. customwas then dried in vacuum

Sources & evidence

ORD record
ord-908bb9680c6647c3b8b43d998c79fce2
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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