Thionyl Chloride → Profluazol

HRID 1934839

Reaction equation

HRID 1934839 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][S:9]([CH2:12][Cl:13])(=[O:11])=[O:10])=[CH:6][C:5]([NH:14][C:15]([N:17]2[CH2:21][C@@H:20]([F:22])[CH2:19][C@@H:18]2[C:23](O)=[O:24])=[O:16])=[C:4]([F:26])[CH:3]=1.S(Cl)(Cl)=O>ClCCl.CN(C)C=O>[Cl:13][CH2:12][S:9]([NH:8][C:7]1[CH:6]=[C:5]([N:14]2[C:23](=[O:24])[C@H:18]3[CH2:19][C@H:20]([F:22])[CH2:21][N:17]3[C:15]2=[O:16])[C:4]([F:26])=[CH:3][C:2]=1[Cl:1])(=[O:10])=[O:11]

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 54019167(2R-trans)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]-4-fluoro-2-pvrrolidinecarboxylic acid

Product 1

HCID 11037075ProfluazolYield 84.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Crude (2R-trans)-1-[[[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]amino]carbonyl]-4-fluoro-2-pyrrolidinecarboxylic acid (173.43 g) was suspended in 550 mL of dichloromethane and 0.65 mL (0.61 g, 8.4 mmol) of N,N-dimethylformamide was added, followed by the dropwise addition of 58 mL (95 g, 0.80 mol) of thionyl chloride at room temperature, and stirring was continued at room temperature. After 2.5 hours, the mixture became homogeneous. After 22 hours, the mixture was poured into 500 mL of ice-water, the layers were separated and the aqueous layer was extracted with dichloromethane (twice with 75 mL). The organic layers were combined, washed with saturated aqueous sodium bicarbonate (twice with 400 mL), dried over magnesium sulfate and evaporated under reduced pressure to afford 140.69 g of the crude title compound (84.7% yield from the isocyanate).

Workup

  1. customwas continued at room temperature
  2. waitAfter 22 hours
  3. customthe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (twice with 75 mL)
  5. washwashed with saturated aqueous sodium bicarbonate (twice with 400 mL),
  6. dry with materialdried over magnesium sulfate
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-f57b8b8f1b3e40a7af08a48584c60376
Source dataset
uspto-grants-2002_05
Patent number
US06384234B1

Linked notes

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