Potassium tert-butoxide → SUN 1334H

HRID 1593372Notes

Reaction equation

HRID 1593372 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[N:9]2[CH2:14][CH2:13][N:12]([CH2:15]/[CH:16]=[CH:17]/[CH2:18][OH:19])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[Cl:33][CH2:34][C:35]([O-:37])=[O:36].[Na+]>C(O)(C)(C)C>[ClH:33].[ClH:33].[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[N:9]2[CH2:10][CH2:11][N:12]([CH2:15]/[CH:16]=[CH:17]/[CH2:18][O:19][CH2:34][C:35]([OH:37])=[O:36])[CH2:13][CH2:14]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 23665759Sodium chloroacetateHCID 66917944HCID 66917944, compound

Product 1

HCID 69509032SUN 1334H

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a stirred solution of 4-{4-[bis-(4-fluorophenyl)methyl]piperazin-1-yl}-(E)-but-2-en-1-ol (247.0 g, 0.689 mol) and potassium tert-butoxide (139.2 g, 1.240 mol) in anhydrous tert-butanol (2000 ml), preheated at 60-65° C. for 1 hr. under nitrogen atmosphere, is added dry sodium chloroacetate (160.5 g, 1.378 mol). The reaction mass is then refluxed for further 5 hrs. The mixture is then concentrated under reduced pressure at below 60° C. until tert-butanol is completely removed. The residue is taken up in water (1500 ml) and washed with ethyl acetate (2×1500 ml). The aqueous solution is then acidified to pH 5-6, extracted into dichloromethane (2×750 ml), washed dichloromethane layer with water (300 ml), and concentrated to get crude product as a foamy solid. The crude product is purified by flash column chromatography on silica gel using toluene-methanol (4:1) as mobile phase. The product was converted to its dihydrochloride salt as in example 17.

Workup

  1. temperatureThe reaction mass is then refluxed for further 5 hrs
  2. concentrationThe mixture is then concentrated under reduced pressure at below 60° C. until tert-butanol
  3. customis completely removed
  4. washwashed with ethyl acetate (2×1500 ml)
  5. extractionextracted into dichloromethane (2×750 ml)
  6. washwashed dichloromethane layer with water (300 ml)
  7. concentrationconcentrated
  8. customto get crude product as a foamy solid
  9. customThe crude product is purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-e44e5448ece2483d9cada542e644385d
Source dataset
uspto-grants-2007_11
Patent number
US07297697B2

Reaction notes

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