Hydrochloric Acid → HCID 117736996, compound

HRID 1474575Notes

Reaction equation

HRID 1474575 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=[O:12].[BH4-].[Na+].Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1C(=O)N([Br:35])C(=O)C1>CO.C1(C)C=CC=CC=1.C1COCC1.[Cl-].[Na+].O.CCOC(C)=O.O>[Br:35][CH:5]1[CH2:4][C:3]2[C:7](=[C:8]([F:11])[CH:9]=[CH:10][C:2]=2[Cl:1])[CH:6]1[OH:12]

Participants

12

Reactant 5

HCID 313Hydrochloric AcidHCID 67184N-bromobutanimideHCID 521998p-Toluenesulfonic acid monohydrateHCID 4311764Sodium borohydrideHCID 916187844-Chloro-7-fluoro-1-indanone

Product 1

HCID 117736996HCID 117736996, compound

Reagents, catalysts & solvents 6

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 4-chloro-7-fluoro-2,3-dihydro-1H-inden-1-one (CAS No. 1260018-63-0, 900 mg, 4.88 mmol) in MeOH (30 mL) was added sodium borohydride (221 mg, 5.85 mmol) at room temperature. The reaction mixture was stirred for 20 minutes at room temperature. To the reaction was added 2N HCl, AcOEt and water at 0° C. The layers were separated. The organic layer was washed with brine and dried over MgSO4, then the solvent was evaporated in vacuo. To a solution of the residue in toluene (50 ml) was added p-toluenesulfonic acid monohydrate (100 mg, 0.53 mmol) and the reaction mixture was refluxed for 20 minutes. After cooling to room temperature, the reaction mixture was passed through NH silicagel and evaporated in vacuo. To a solution of the residue in THF (30 ml) and water (10 ml) was added NBS (842 mg, 4.73 mmol) and the reaction mixture was stirred for 20 hours at room temperature. AcOEt and brine were added to the mixture, and the layers were separated. The organic layer was successively washed with saturated aqueous Na2S2O3 and brine and then dried over MgSO4. The solvent was evaporated in vacuo. The residue was purified by silicagel flash column chromatography (Yamazen HI-FLASH™ column L size, 40 mL/min, gradient 0% to 40% AcOEt in n-heptane) to afford the title compound (675 mg, 2.54 mmol).

Workup

  1. customThe layers were separated
  2. washThe organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. customthe solvent was evaporated in vacuo
  5. temperaturethe reaction mixture was refluxed for 20 minutes
  6. temperatureAfter cooling to room temperature
  7. customevaporated in vacuo
  8. stirringthe reaction mixture was stirred for 20 hours at room temperature
  9. customthe layers were separated
  10. washThe organic layer was successively washed with saturated aqueous Na2S2O3 and brine
  11. dry with materialdried over MgSO4
  12. customThe solvent was evaporated in vacuo
  13. customThe residue was purified by silicagel flash column chromatography (Yamazen HI-FLASH™ column L size, 40 mL/min, gradient 0% to 40% AcOEt in n-heptane)

Sources & evidence

ORD record
ord-8cc01092a6e743718dea72893acab4b6
Source dataset
uspto-grants-2015_04
Patent number
US09018260B2

Reaction notes

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