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Hydrochloric Acid → N-[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]acetamide

HRID 432949
Notes
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Reaction equation

HRID 432949 reaction equation
[NH2:1][C:2]1[C:3]([Cl:13])=[CH:4][C:5]([F:12])=[C:6]([NH:8][C:9](=[O:11])[CH3:10])[CH:7]=1.N1C=CC=CC=1.[Cl:20][CH2:21][S:22](Cl)(=[O:24])=[O:23].Cl>O.C(OCC)(=O)C>[Cl:13][C:3]1[C:2]([NH:1][S:22]([CH2:21][Cl:20])(=[O:24])=[O:23])=[CH:7][C:6]([NH:8][C:9](=[O:11])[CH3:10])=[C:5]([F:12])[CH:4]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 77054(Chloromethyl)sulfonyl chlorideHCID 11769584N-(5-amino-4-chloro-2-fluorophenyl)acetamide

Product 1

HCID 10870764N-[4-chloro-5-[[(chloromethyl)sulfonyl]amino]-2-fluorophenyl]acetamide

Reagents, catalysts & solvents 2

HCID 962
Water
Solvent
HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

1000 g of crude N-(5-amino4-chloro-2-fluorophenyl)acetamide (4.93 mol) which still contained 1 L of ethyl acetate was dissolved in 3900 g (49.3 mol) of pyridine at 20° C. To the yellow solution was added 845 g (5.42 mol) of chloromethanesulfonyl chloride at 20-30° C. over 1-2 hours. The solution was allowed to stir for 1 additional hour. 2300 g of pyridine were distilled off under reduced pressure at 40° C. To the remaining reaction mixture were added 5.3 L of water and 1.7 L of concentrated HCl (pH 3) whereupon the product precipitated. The slurry was cooled to 20° C. and filtered off. The filter cake was washed twice with 1300 mL of water. The product was dried in vacuo at 70° C. to yield 1500 g (92% purity) of the title compound as a solid melting at 210° C.

Workup

  1. distillation2300 g of pyridine were distilled off under reduced pressure at 40° C
  2. customTo the remaining reaction mixture
  3. customprecipitated
  4. filtrationfiltered off
  5. washThe filter cake was washed twice with 1300 mL of water
  6. customThe product was dried in vacuo at 70° C.

Sources & evidence

ORD record
ord-1b9db3bfb50640d98ef2300492be3d1a
Source dataset
uspto-grants-2003_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06664400B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes