Ammonia → HCID 86759288, compound

HRID 431264Notes

Reaction equation

HRID 431264 reaction equation
Cl.C([N:9]1[CH2:14][CH2:13][C@@H:12]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[C@H:11]([CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]3[O:30][CH2:31][O:32][C:26]=3[CH:25]=2)[CH2:10]1)C1C=CC=CC=1.C(Cl)(Cl)Cl.N.[C:38]([OH:47])(=[O:46])[C@H:39]([C@@H:41]([C:43]([OH:45])=[O:44])[OH:42])[OH:40]>CO.O>[C:38]([OH:47])(=[O:46])[C@H:39]([C@@H:41]([C:43]([OH:45])=[O:44])[OH:42])[OH:40].[F:21][C:18]1[CH:19]=[CH:20][C:15]([C@@H:12]2[CH2:13][CH2:14][NH:9][CH2:10][C@H:11]2[CH2:22][O:23][C:24]2[CH:29]=[CH:28][C:27]3[O:30][CH2:31][O:32][C:26]=3[CH:25]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6212ChloroformHCID 439655D-Tartaric acidHCID 70030311(3S,4R)-3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)-1-(phenylmethyl)piperidine hydrochloride (1:1)

Product 1

HCID 86759288HCID 86759288, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A suspension containing 9.1 g (0.02 mol) of (±)-trans-1-benzyl-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)piperidine hydrochloride in the mixture of 100 ml of chloroform and 50 ml of water is alkalinized to pH 9 by adding concentrated aqueous ammonia solution. After separation of the phases, the aqueous layer is extracted with 20 ml of chloroform. The combined organic phase is dried over magnesium sulfate and, after filtering the drying agent the solution is evaporated to solvent-free. The evaporation residue is dissolved in 120 ml of ethanol and hydrogenated in an autoclave in the presence of 0.8 g of 10% palladium-on-carbon catalyst at 40° C., under 5×105 Pa pressure for 2 to 3 hours. After taking up the hydrogen, the catalyst is filtered and the filtrate is evaporated to solvent-free. The evaporation residue (weighing 6.6 g) is dissolved in 80 ml of methanol, a solution of 3 g (0.02 mol) of (+)-D-tartaric acid in 20 ml of methanol is added at room temperature and the mixture is stirred for 5 hours. The precipitated crystalline product is filtered to yield 3.2 g (66%) of (−)-trans-4-(4-flurophenyl)-3-(3,4-metylenedioxyphenoxymethyl)piperidine (+)-D-tartarate, m.p.: 178-180° C.; [α]D20−50.5° (c=1, dimethylformamide).

Workup

  1. customAfter separation of the phases
  2. extractionthe aqueous layer is extracted with 20 ml of chloroform
  3. dry with materialThe combined organic phase is dried over magnesium sulfate
  4. filtrationafter filtering the drying agent the solution
  5. customis evaporated to solvent-free
  6. dissolutionThe evaporation residue is dissolved in 120 ml of ethanol
  7. filtrationthe catalyst is filtered
  8. customthe filtrate is evaporated to solvent-free
  9. dissolutionThe evaporation residue (weighing 6.6 g) is dissolved in 80 ml of methanol
  10. filtrationThe precipitated crystalline product is filtered

Sources & evidence

ORD record
ord-3738e8b848a5452a8f6a11656c788c15
Source dataset
uspto-grants-2003_12
Patent number
US06657062B1

Reaction notes

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