Dichloromethane → HCID 89655984, compound

HRID 930946Notes

Reaction equation

HRID 930946 reaction equation
C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[C:16]([O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])=[CH:15][C:11]([C:12](O)=[O:13])=[C:10]([NH:26][S:27]([CH2:30][CH3:31])(=[O:29])=[O:28])[CH:9]=1.ClCCl.[OH-].[NH4+:36]>C(OCC)(=O)C.CN(C)C=O>[Br:7][C:8]1[C:16]([O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])=[CH:15][C:11]([C:12]([NH2:36])=[O:13])=[C:10]([NH:26][S:27]([CH2:30][CH3:31])(=[O:29])=[O:28])[CH:9]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14923Ammonium HydroxideHCID 65578Oxalyl chlorideHCID 89656127HCID 89656127, compound

Product 1

HCID 89655984HCID 89655984, compoundYield 82.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Oxalyl chloride (0.046 mL, 0.54 mmol) was added dropwise to a suspension of Example 324d (214 mg, 0.49 mmol) and dichloromethane (2.2 mL). 1 Drop dimethylformamide was added and the reaction mixture was stirred at ambient temperature for 2 hours. The solvent was evaporated and the residue was dried (in-vacuo). The resulting acid chloride was suspended in tetrahydrofuran (1.0 mL) and was cooled to 0° C. as ammonium hydroxide (0.65 mL, 4.7 mmol) was added dropwise. The reaction mixture was stirred at ambient temperature for 2 hours. Ethyl acetate was added and the solution was washed with water, saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 1-8% methanol/dichloromethane gradient) to afford the title compound (176 mg, 82% yield).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was dried (in-vacuo)
  3. additionwas added dropwise
  4. stirringThe reaction mixture was stirred at ambient temperature for 2 hours
  5. washthe solution was washed with water, saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (silica gel, 1-8% methanol/dichloromethane gradient)

Sources & evidence

ORD record
ord-3365530235b84745ada3f7f6da476dad
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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