Hydrogen Bromide → (+)-Cis-1-methyl-3-ethoxymethyl-4-(3,4-dichlorophenyl)-piperidine hydrobromide

HRID 227573Notes

Reaction equation

HRID 227573 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C@H:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=2)[C@H:4]([CH2:16][O:17][CH2:18][CH3:19])[CH2:3]1.C(C(C(O)=O)(O)C(C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[BrH:46]>C(O)C.[OH-].[Na+].C(OCC)C>[BrH:46].[CH3:1][N:2]1[CH2:7][CH2:6][C@H:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=2)[C@H:4]([CH2:16][O:17][CH2:18][CH3:19])[CH2:3]1

Participants

7

Reactant 3

HCID 260Hydrogen BromideHCID 12362975HCID 12362975, compoundHCID 68533369(+/-)-Cis-1-methyl-3-ethoxymethyl-4-(3,4-dichlorophenyl)-piperidine

Product 1

HCID 68534666(+)-Cis-1-methyl-3-ethoxymethyl-4-(3,4-dichlorophenyl)-piperidine hydrobromideYield 30.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 14798Sodium HydroxideSolvent

Procedure

(±)-Cis-1-methyl-3-ethoxymethyl-4-(3,4-dichlorophenyl)-piperidine (9) (1.1 g, 3.7 mmol) and (−)-dibenzoyltartaric acid (0.48 g, 1.3 mmol) were dissolved in 99% ethanol (10 ml) and evaporated to dryness. The evaporation residue was crystallized from toluene (3 ml). Recrystallized from a mixture of toluene (10 ml) and ethanol (10 ml). The precipitate was isolated and dissolved in a mixture of 4 N NaOH (5 ml) and diethyl ether (10 ml). The diethyl ether was separated and dried with magnesium sulfate yielding 0.25 g (45%) of the product as the free base. Hydrobromic acid (0.20 ml, 1.7 mmol) was added and the mixture evaporated to dryness. The residue was recrystallized from ethanol (2 ml) and diethyl ether (10 ml) to yield 0.20 g (28%) of (13), mp 183-185° C., [α]D25=+62.8°, (c=14 mg/ml in 99% ethanol).

Workup

  1. customevaporated to dryness
  2. customThe evaporation residue was crystallized from toluene (3 ml)
  3. customRecrystallized from a mixture of toluene (10 ml) and ethanol (10 ml)
  4. customThe precipitate was isolated
  5. customThe diethyl ether was separated
  6. dry with materialdried with magnesium sulfate yielding 0.25 g (45%) of the product as the free base
  7. customthe mixture evaporated to dryness
  8. customThe residue was recrystallized from ethanol (2 ml) and diethyl ether (10 ml)

Sources & evidence

ORD record
ord-f57b696915a940bc855d76dd41447e00
Source dataset
uspto-grants-2009_07
Patent number
US07560562B2

Reaction notes

Loading…