Hydrochloric Acid → HCID 10480187, compound

HRID 981283Notes

Reaction equation

HRID 981283 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1([C:15]2[C:16]([F:36])=[CH:17][C:18]3[C:29](=[O:30])[C:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:27][N:20]4[CH:21]([CH2:25]O)[CH2:22][O:23][C:24]=2[C:19]=34)[CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O.Cl.N12CCCN=C1CCCCC2>C(Cl)Cl.O.C(OCC)(=O)C.C1C=CC=CC=1.C(N(CC)CC)C>[CH2:1]([O:8][C:9]([NH:11][C:12]1([C:15]2[C:16]([F:36])=[CH:17][C:18]3[C:29](=[O:30])[C:28]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:27][N:20]4[C:21](=[CH2:25])[CH2:22][O:23][C:24]=2[C:19]=34)[CH2:13][CH2:14]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 313Hydrochloric Acid2×HCID 31297Methanesulfonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10323548HCID 10323548, compound

Product 1

HCID 10480187HCID 10480187, compoundYield 71%

Reagents, catalysts & solvents 5

HCID 241BenzeneSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 4 ml of methylene chloride was suspended 380 mg of ethyl 10-(1-benzyloxycarbonylaminocyclopropyl)-9-fluoro-3-hydroxymethyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3de][1,4]benzoxazine-6-carboxylate. To the resulting suspension were added, with ice-cooling, 230 mg of triethylamine and 260 mg of methanesulfonyl chloride in this order. The resulting mixture was stirred at room temperature for 30 minutes. To the reaction mixture were added 10 ml of methylene chloride and 10 ml of water in this order. The resulting mixture was adjusted to pH 1 with 2N hydrochloric acid. The organic layer was separated, washed with water and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. To the residue obtained were added 4.4 ml of benzene and 175 mg of 1,8-diazabicyclo-[5,4,0]undec-7-ene in this order. The resulting mixture was refluxed for 1 hour. The reaction mixture was added to a mixture of 20 ml of ethyl acetate and 20 ml of water. The resulting mixture was adjusted to pH 1 with 2N hydrochloric acid. The organic layer was separated, washed with water and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue obtained was purified by a column chromatography (eluant: toluene/ethyl acetate=3/2) to obtain 260 mg (yield: 71.0%) of ethyl 10-(1-benzyloxycarbonylaminocyclopropyl)-9-fluoro-3-methylene-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]-benzoxazine-6-carboxylate.

Workup

  1. additionTo the resulting suspension were added, with ice-
  2. temperaturecooling
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materiala saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate
  6. customThe solvent was removed by distillation under reduced pressure
  7. customTo the residue obtained
  8. temperatureThe resulting mixture was refluxed for 1 hour
  9. customThe organic layer was separated
  10. washwashed with water
  11. dry with materiala saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate
  12. customThe solvent was removed by distillation under reduced pressure
  13. customThe residue obtained
  14. customwas purified by a column chromatography (eluant: toluene/ethyl acetate=3/2)

Sources & evidence

ORD record
ord-97aa9fab6ecc4e269a9a33aa9f9227b5
Source dataset
uspto-grants-1991_02
Patent number
US04990508

Reaction notes

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