Chloroacetyl chloride → HCID 69701133, compound

HRID 1596091Notes

Reaction equation

HRID 1596091 reaction equation
C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[Cl:12][C:13]1[CH:14]=[C:15]([CH:20](O)[C@H:21]([OH:44])[CH2:22][CH2:23][O:24][C:25]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:16]=[CH:17][C:18]=1[Cl:19].O.O.O.Cl([O-])(=O)(=O)=O.[Li+].[CH:55]1([CH2:61][NH2:62])[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]1.C(N(CC)CC)C.[Cl:70][CH2:71][C:72](Cl)=[O:73]>N1C=CC=CC=1.C(Cl)Cl.C(OCC)(=O)C.O>[C:38]1([C:25]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:24][CH2:23][CH2:22][C@@H:21]([OH:44])[CH:20]([C:15]2[CH:16]=[CH:17][C:18]([Cl:19])=[C:13]([Cl:12])[CH:14]=2)[N:62]([C:72](=[O:73])[CH2:71][Cl:70])[CH2:61][CH:55]2[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

11

Reactant 6

HCID 6577Chloroacetyl chlorideHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 76688CyclohexanemethylamineHCID 23708903Lithium perchlorate trihydrateHCID 53669173HCID 53669173, compound

Product 1

HCID 69701133HCID 69701133, compoundYield 63%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

p-Toluenesulfonyl chloride (2.03g, 10.7 mmol) was added to a solution of (2R)-(3,4-dichlorophenyl)-4-(triphenylmethoxy)butan-1,2-diol (3.51 g, 7.11 mmol), which was prepared in Example 12(a), in pyridine (17 ml). The mixture was stirred at room temperature overnight. To the reaction mixture, water was added and it was extracted with ethyl acetate. The organic layer was dried over anydrous magnesium sulfate and then the solvent was distilled off under reduced pressure. The residue was dissolved in acetonitrile (50 ml) and lithium perchlorate trihydrate (3.42 g. 21.3 mmol) and cyclohexylmethylamine (2.78 ml, 21.3 mmol) were added to the solution. The mixture was stirred at 100° C. overnight. Ethyl acetate was added to the reaction mixture and it was washed with a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate and then the solvent was distilled off under reduced pressure. A half of the residue by weight was dissolved in methylene chloride (30 ml). To this solution, triethylamine (2.48 ml, 17.8 mmol) and chloroacetyl chloride (1.42 ml, 17.8 mmol) were added with ice-cooling. The mixture was stirred at 0° C. for 1 hour. To the reaction mixture, methylene chloride was added, the organic layer was washed with water and then with a saturated aquoeus solution of sodium chloride and was dried over anhydrous magnesium sulfate. After distillation under reduced pressure, the resulting residue was purified by flash chromatography on a silica gel column using n-hexane/ethyl acetate=20/1−10/1 as an eluant to afford the title compound (1.49 g, 63%).

Workup

  1. extractionit was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anydrous magnesium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. dissolutionThe residue was dissolved in acetonitrile (50 ml)
  5. stirringThe mixture was stirred at 100° C. overnight
  6. washwas washed with a saturated aqueous solution of sodium chloride
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. dissolutionA half of the residue by weight was dissolved in methylene chloride (30 ml)
  10. temperaturecooling
  11. stirringThe mixture was stirred at 0° C. for 1 hour
  12. washthe organic layer was washed with water
  13. dry with materialwith a saturated aquoeus solution of sodium chloride and was dried over anhydrous magnesium sulfate
  14. distillationAfter distillation under reduced pressure
  15. customthe resulting residue was purified by flash chromatography on a silica gel column

Sources & evidence

ORD record
ord-923e8a331ff8427a91628567e3f39522
Source dataset
uspto-grants-2001_09
Patent number
US06288059B1

Reaction notes

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