Dimethyl Sulfide → HCID 57112871, compound

HRID 376272Notes

Reaction equation

HRID 376272 reaction equation
Cl.Cl.C[O:4][C:5]1[CH:24]=[CH:23][C:22]([N:25]2[C:29]([C:30]([F:33])([F:32])[F:31])=[N:28][N:27]=[N:26]2)=[CH:21][C:6]=1[CH2:7][NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][NH:11][C@H:10]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C.B(Br)(Br)Br.CSC>C(Cl)(Cl)Cl.CO>[OH:4][C:5]1[CH:24]=[CH:23][C:22]([N:25]2[C:29]([C:30]([F:33])([F:32])[F:31])=[N:28][N:27]=[N:26]2)=[CH:21][C:6]=1[CH2:7][NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][NH:11][C@H:10]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 1068Dimethyl SulfideHCID 8471TriethylamineHCID 25134Boron tribromideHCID 6918330Vofopitant dihydrochloride

Product 1

HCID 57112871HCID 57112871, compoundYield 80.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A suspension of [2-methoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-([2S,3S]-2-phenylpiperidin-3yi)amine dihydrochloride (1.01 g, 2 mmol) in chloroform (20ml) was stirred at room temperature and treated with triethylamine, (0.58 ml, 406 mg, 4 mmol) to give a clear solution. This was then treated slowly with a solution of boron tribromide: dimethylsulfide complex (20 ml of 1M solution in dichloromethane; 20 mmol) and the reaction mixture was refluxed under nitrogen for 3 days. Further reagent (10 ml, 10 mmol) was then added and after a further 3 days the mixture was cooled in an ice-bath, stirred and treated with methanol (40 ml ). The mixture was evaporated to dryness. This treatment was repeated twice further. The resulting oil was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium bicarbonate (100 ml). The aqueous phase was extracted with further ethyl acetate (50 ml) after pH adjustment (to pH ca 8). Combined extracts were washed with brine (100 ml) dried (MgSO4) and evaporated to a brown foam, which was chromatographed on silica (Merck 9385) eluting with 2% then 5% methanol in dichloromethane. The required fractions were combined and evaporated to give the title compound as a light brown foam (672 mg), mass spectrum (thermospray +ve) m/e 419 (MH+).

Workup

  1. customto give a clear solution
  2. temperaturewas cooled in an ice-bath
  3. stirringstirred
  4. customThe mixture was evaporated to dryness
  5. customThe resulting oil was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium bicarbonate (100 ml)
  6. extractionThe aqueous phase was extracted with further ethyl acetate (50 ml) after pH adjustment (to pH ca 8)
  7. washCombined extracts were washed with brine (100 ml)
  8. dry with materialdried (MgSO4)
  9. customevaporated to a brown foam, which
  10. customwas chromatographed on silica (Merck 9385)
  11. washeluting with 2%
  12. customevaporated

Sources & evidence

ORD record
ord-7c03d1ebb2d6453c9a7df8ee511a9f03
Source dataset
uspto-grants-2000_02
Patent number
US06020346

Reaction notes

Loading…