Acetonitrile → 2-Propenoic acid, 3-[3-[(phenylaMino)sulfonyl]phenyl]-, (2E)-

HRID 239811Notes

Reaction equation

HRID 239811 reaction equation
[F-].[K+].[C:3]1([NH:9][S:10]([C:13]2[CH:14]=[C:15](/[CH:19]=[CH:20]/[C:21]([OH:23])=[O:22])[CH:16]=[CH:17][CH:18]=2)(=[O:12])=[O:11])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:24](#N)[CH3:25]>>[C:3]1([NH:9][S:10]([C:13]2[CH:14]=[C:15](/[CH:19]=[CH:20]/[C:21]([OH:23])=[O:22])[CH:16]=[CH:17][CH:18]=2)(=[O:12])=[O:11])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1.[CH2:24]([O:22][C:21](=[O:23])/[CH:20]=[CH:19]/[C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([S:10](=[O:12])(=[O:11])[NH:9][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:14]=1)[CH3:25]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 522689Potassium FluorideHCID 224924412-Propenoic acid, 3-[3-[(phenylaMino)sulfonyl]phenyl]-, (2E)-

Product 2

HCID 224924412-Propenoic acid, 3-[3-[(phenylaMino)sulfonyl]phenyl]-, (2E)-HCID 53487508HCID 53487508, compound

Conditions

Temperature
80 °C

Procedure

To the 30 gallon (˜136 L) reactor was charged the (E)-3-(3-phenylsulfamoyl-phenyl)-acrylic acid ethyl ester (5) (4.48 kg; 331.39 g/mol; 13.5 mol) along with 2 M aqueous sodium hydroxide (17.76 L; ˜35 mol). The mixture was heated to 40-50° C. and held at this temperature for 2 hours before sampling, at which point the reaction was deemed to be complete with no compound (5) being detected by HPLC. The batch was adjusted to pH 2.2 using 1 M aqueous hydrochloric acid while maintaining the batch temperature between 40-50° C. The product had precipitated and the batch was cooled to 20-30° C. and held at this temperature for 1 hour before filtering and washing the cake with water (8.9 L). The filtrate was discarded. The batch was allowed to condition on the filter overnight before being charged back into the reactor and slurried in water (44.4 L) at 40-50° C. for 2 hours. The batch was cooled to 15-20° C., held for 1 hour, and then filtered and the residue washed with water (8.9 L). The filtrate was discarded. The crude title compound (6) was transferred to an oven for drying at 45-55° C. under vacuum with a slight nitrogen bleed for 5 days (this was done for convenience) to give a white solid (3.93 kg, 97% yield). The moisture content of the crude material was measured using Karl Fischer (KF) titration and found to be <0.1% (w/w). To the 30 gallon (˜136 L) reactor was charged the crude compound (6) along with acetonitrile (47.2 L). The batch was heated to reflux (about 80° C.) and held at reflux for 2 hours before cooling to 0-10° C. and holding at this temperature overnight in order to precipitate the product. The batch was filtered and the residue was washed with cold acetonitrile (7.9 L). The filtrate was discarded and the residue was dried under vacuum at 45-55° C. for 21.5 hours. The title compound (6) was obtained as a fluffy white solid (3.37 kg, 84% yield with respect to compound (5)) with a purity of 99.89% (AUC) by HPLC.

Workup

  1. temperatureThe batch was heated
  2. temperatureat reflux for 2 hours
  3. temperaturebefore cooling to 0-10° C.
  4. customholding at this temperature overnight in order
  5. customto precipitate the product
  6. filtrationThe batch was filtered
  7. washthe residue was washed with cold acetonitrile (7.9 L)
  8. customthe residue was dried under vacuum at 45-55° C. for 21.5 hours

Sources & evidence

ORD record
ord-bec593759914456e94a3101ae609393f
Source dataset
uspto-grants-2014_02
Patent number
US08642809B2

Reaction notes

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