Carbon tetrabromide → HCID 19360610, compound

HRID 376979Notes

Reaction equation

HRID 376979 reaction equation
O[CH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([CH3:21])([CH3:20])[C:10]([C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)=[O:11])[CH2:4]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br.C([O-])(=[S:48])C.[K+]>C(Cl)Cl.CC(N(C)C)=O.C(O)C>[SH:48][CH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([CH3:21])([CH3:20])[C:10]([C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)=[O:11])[CH2:4]1

Participants

8

Reactant 4

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 19360632HCID 19360632, compoundHCID 23670855Potassium ethanethioate

Product 1

HCID 19360610HCID 19360610, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

10.2 g (0.33 mol) of 2-(3-hydroxymethyl-piperidin-1-yl)-2-methyl-1-[4-(methylthio)-phenyl]-propan-1-one and 10.5 g of triphenylphosphine are dissolved in 60 ml of methylene chloride. 13.3 g of carbon tetrabromide is dissolved in 15 ml of methylene chloride and is added dropwise to the above solution at 5 ° C. After stirring for 2 h, the resulting solution is concentrated to give a slurry. This material is purified by column chromatography on silica gel with ethyl acetate-hexane (50-50) as an eluent, and an oily product is obtained. The resulting material is used for the next reaction. 13.0 g of the above oily product is dissolved in 80 ml of dried dimethylacetamide and 4.95 g of potassium thioacetate is added. After stirring for 2.5 h at 50 ° C., the reaction mixture is poured into ice-water and extracted with ethyl acetate. The combined organic layer is washed with saturated sodium chloride solution and died over MgSO4. The solvent is removed by evaporator and the crude oil is further purified by column chromatography on silica gel with ethyl acetate-hexane (10:90) as an eluent, and an oily product is obtained. The product is dissolved in 40 ml of ethanol and the solution is bubbled by nitrogen for 10 min. to remove oxygen. To the solution are added 10 ml of 2N sodium hydroxide solution and stirred at 0° C. for 1 h. After the reaction mixture is neutralized by adding 2N hydrochloric acid solution, the resulting solution is poured into 10 ml of water and extracted with ethyl acetate. The organic layer is washed with water and saturated sodium chloride solution, and dried over MgSO4. After ethyl acetate is distilled off, the residue is purified by means of column chromatography on silica gel with ethyl acetate-hexane (5-95) as an eluent, and an oily product is obtained. The structure is confirmed by the 1H-NMR spectrum (CDCl3): δ [ppm] 1.02 (m, 1H), 1.26 (t, 1H), 1.29 (s, 3H), 1.30 (s, 3H), 1.43-1.55 (m, 1H), 1.61-1.66 (m, 2H), 1.87 (m, 1H), 2.06 (m, 1H), 2.23 (m, 1H), 2.40 (t, 2H), 2.52 (s, 3H), 2.69 (m, 1H), 2.88 (d, 1H), 7.22 (d, 2H), 8.49 (d, 2H).

Workup

  1. additionis added dropwise to the above solution at 5 ° C
  2. concentrationthe resulting solution is concentrated
  3. customto give a slurry
  4. customThis material is purified by column chromatography on silica gel with ethyl acetate-hexane (50-50) as an eluent
  5. customan oily product is obtained
  6. customThe resulting material is used for the next reaction
  7. stirringAfter stirring for 2.5 h at 50 ° C.
  8. extractionextracted with ethyl acetate
  9. washThe combined organic layer is washed with saturated sodium chloride solution
  10. customThe solvent is removed by evaporator
  11. customthe crude oil is further purified by column chromatography on silica gel with ethyl acetate-hexane (10:90) as an eluent
  12. customan oily product is obtained
  13. customthe solution is bubbled by nitrogen for 10 min.
  14. customto remove oxygen
  15. additionTo the solution are added 10 ml of 2N sodium hydroxide solution
  16. stirringstirred at 0° C. for 1 h
  17. additionby adding 2N hydrochloric acid solution
  18. additionthe resulting solution is poured into 10 ml of water
  19. extractionextracted with ethyl acetate
  20. washThe organic layer is washed with water and saturated sodium chloride solution
  21. dry with materialdried over MgSO4
  22. distillationAfter ethyl acetate is distilled off
  23. customthe residue is purified by means of column chromatography on silica gel with ethyl acetate-hexane (5-95) as an eluent
  24. customan oily product is obtained

Sources & evidence

ORD record
ord-d17237cd0f8b4c25aad0f67be7cfae97
Source dataset
uspto-grants-2000_02
Patent number
US06022906

Reaction notes

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