Ammonium Chloride → 1-(2,4-Difluorophenyl)-1-(6-cyanobenzothiazol-2-YL)-2-chloroethanol

HRID 265328

Reaction equation

HRID 265328 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]2[N:7]=[CH:8][S:9][C:5]=2[CH:4]=1)#[N:2].C([Li])CCC.[Cl:17][CH2:18][C:19]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28])=[O:20].[Cl-].[NH4+]>O1CCCC1.CCCCCC>[F:28][C:22]1[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:21]=1[C:19]([C:8]1[S:9][C:5]2[CH:4]=[C:3]([C:1]#[N:2])[CH:11]=[CH:10][C:6]=2[N:7]=1)([OH:20])[CH2:18][Cl:17]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 5880832-Chloro-1-(2,4-difluorophenyl)ethanoneHCID 10607144Benzothiazole-6-carbonitrileHCID 178418339Butyllithium

Product 1

HCID 105940491-(2,4-Difluorophenyl)-1-(6-cyanobenzothiazol-2-YL)-2-chloroethanolYield 42.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-98 °C

Procedure

After 6-cyanobenzothiazole (1.60 g) was dissolved in tetrahydrofuran (80 ml), and the solution was cooled to -98° C. in a nitrogen atmosphere, a 1.6M solution (5.9 ml) of n-butyllithium in hexane was added dropwise over 10 minutes, and the resultant mixture was stirred for 5 minutes. A solution of 2-chloro-2',4'-difluoroacetophenone (2.85 g) in tetrahydrofuran (20 ml) was added dropwise to this mixture. After the liquid reaction mixture was heated to -10° C., an aqueous solution of ammonium chloride was added thereto. After the mixture was heated to room temperature, an organic layer was taken out, and the solvent was distilled out under reduced pressure. A water layer was extracted with ethyl acetate and the extract was then put together with the residue of the organic layer. This organic layer was washed with water and then with saturated saline, dried over magnesium sulfate and then distilled under reduced pressure. The residue was subjected to column chromatography on silica gel (solvent: hexane/ethyl acetate=20/1, next, hexane/ethyl acetate=5/1), thereby obtaining the intended compound (1.49 g).

Workup

  1. customAfter the liquid reaction mixture
  2. temperaturewas heated to -10° C.
  3. temperatureAfter the mixture was heated to room temperature
  4. distillationthe solvent was distilled out under reduced pressure
  5. extractionA water layer was extracted with ethyl acetate
  6. washThis organic layer was washed with water
  7. dry with materialwith saturated saline, dried over magnesium sulfate
  8. distillationdistilled under reduced pressure

Sources & evidence

ORD record
ord-84cccc5a62694306bd4487cd32fc6f1e
Source dataset
uspto-grants-1997_07
Patent number
US05648372

Linked notes

Loading…