2,5-Dichloronitrobenzene → (-)-4-[4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(2-nitro-4-chlorophenoxymethyl)-benzonitrile hydrochloride

HRID 1669964Notes

Reaction equation

HRID 1669964 reaction equation
[CH3:1][N:2]([CH3:25])[CH2:3][CH2:4][CH2:5][C@@:6]([C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[CH2:23][OH:24])([C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=1)[OH:7].CC(C)([O-])C.[K+].[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=1[N+:40]([O-:42])=[O:41]>C1COCC1>[ClH:32].[CH3:25][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][C:6]([C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[CH2:23][O:24][C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=1[N+:40]([O-:42])=[O:41])([C:8]1[CH:9]=[CH:10][C:11]([F:14])=[CH:12][CH:13]=1)[OH:7]

Participants

5

Reactant 3

HCID 69772,5-DichloronitrobenzeneHCID 7472057Citadiol, (S)-HCID 23665647Potassium tert-butoxide

Product 1

HCID 67244927(-)-4-[4-(Dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(2-nitro-4-chlorophenoxymethyl)-benzonitrile hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5.6 gm of (S)-(−)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile in 85 ml THF was added 2.02 gm of potassium tertiary butoxide at 0-10° C. and stirred for 10 min. 3.14 gm of 2,5-dichloronitrobenzene was added to the reaction mixture at 0-10° C. and stirred for 10-15 hrs at RT (30-35° C.), solvent distilled under vacuum and 40 ml of water was added, and extracted with toluene, toluene layer was washed with water and 10% sodium hydroxide solution and distilled to get an oily product, which is purified by column chromatography using silica gel and ethylacetate, Wt: 500 mg. The above oily product was dissolved in 10 ml of isopropanol (IPA) at 30° C. and 2.0 ml of IPA-HCl was added, stirred and solvent distilled under vacuum and crystallized in IPA to get (−)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(2-nitro-4-chlorophenoxymethyl)-benzonitrile hydrochloride whose structure was confirmed by IR, NMR and Mass spectral data.

Workup

  1. stirringstirred for 10-15 hrs at RT (30-35° C.), solvent
  2. distillationdistilled under vacuum and 40 ml of water
  3. additionwas added
  4. extractionextracted with toluene, toluene layer
  5. washwas washed with water and 10% sodium hydroxide solution
  6. distillationdistilled
  7. customto get an oily product, which
  8. customis purified by column chromatography
  9. dissolutionThe above oily product was dissolved in 10 ml of isopropanol (IPA) at 30° C.
  10. addition2.0 ml of IPA-HCl was added
  11. stirringstirred
  12. distillationsolvent distilled under vacuum
  13. customcrystallized in IPA

Sources & evidence

ORD record
ord-7559cd04fe184fa5ae861918e0e4f367
Source dataset
uspto-grants-2011_08
Patent number
US07989645B2

Reaction notes

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