Hydrochloric Acid → HCID 131727638, compound

HRID 734385Notes

Reaction equation

HRID 734385 reaction equation
[NH:1]([C:3]([NH:5][CH2:6][C@H:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)=[O:14])[CH2:9][C@H:8]1[F:24])=[S:4])[NH2:2].[CH:25](OCC)(OCC)OCC.Cl>C(O)C>[F:24][C@H:8]1[C@@H:7]([CH2:6][NH:5][C:3]2[S:4][CH:25]=[N:2][N:1]=2)[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=2)=[O:14])[CH2:9]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 31214Ethyl orthoformateHCID 131727639HCID 131727639, compound

Product 1

HCID 131727638HCID 131727638, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of (±)-cis 4-methylbenzyl 4-{[(hydrazinocarbonothioyl) amino]methyl}-3-fluoropiperidine-1-carboxylate (180 mg, 0.51 mmol) in ethanol (10 mL) was treated with triethyl orthoformate (151 mg, 1.02 mmol) and concentrated HCl (0.01 mL) and stirred at room temperature, under nitrogen, for 18 h. After all solids had dissolved, the reaction mixture was heated to reflux for 1.5 hour, cooled to room temperature and the volatiles evaporated. The residue was partitioned between ethyl acetate and dilute sodium bicarbonate solution, the organic layer washed with brine, dried over sodium sulfate and solvent evaporated. The crude product was purified by gradient elution on silica gel (50% ethyl acetate: hexane to 20% methanol: ethyl acetate) to give the title compound as a white solid. The (−)-enantiomer was separated and the hydrochloride salt formed as described in Examples 1 and 2 Step 7.

Workup

  1. dissolutionAfter all solids had dissolved
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for 1.5 hour
  4. temperaturecooled to room temperature
  5. customthe volatiles evaporated
  6. customThe residue was partitioned between ethyl acetate and dilute sodium bicarbonate solution
  7. washthe organic layer washed with brine
  8. dry with materialdried over sodium sulfate and solvent
  9. customevaporated
  10. customThe crude product was purified by gradient elution on silica gel (50% ethyl acetate: hexane to 20% methanol: ethyl acetate)

Sources & evidence

ORD record
ord-2e90e926cfdf4d4194b546b6db4effe2
Source dataset
uspto-grants-2009_09
Patent number
US07592360B2

Reaction notes

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