Diiodomethane → 4-Phenyl-4-[(1-(3,5-bis(trifluoromethyl)phenyl)cyclopropyloxy)methyl]piperidine Hydrochloride

HRID 962486

Reaction equation

HRID 962486 reaction equation
[ClH:1].[C:2]1([C:8]2([CH2:14][O:15][CH:16]([C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([C:29]([F:32])([F:31])[F:30])[CH:20]=3)[CH2:17]O)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:33]([Zn]CC)C.ICI>CCOCC.C(OCC)(=O)C.Cl.CCOCC>[ClH:1].[C:2]1([C:8]2([CH2:14][O:15][C:16]3([C:19]4[CH:20]=[C:21]([C:29]([F:31])([F:30])[F:32])[CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=4)[CH2:17][CH2:33]3)[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 6346DiiodomethaneHCID 190847004-Phenyl-4-((1-(3,5-bis(trifluoromethyl)phenyl)-2-hydroxyethoxy) methyl)piperidine HydrochlorideHCID 178418750HCID 178418750, compound

Product 1

HCID 190846904-Phenyl-4-[(1-(3,5-bis(trifluoromethyl)phenyl)cyclopropyloxy)methyl]piperidine Hydrochloride

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolventHCID 10953452Ether hydrochlorideSolvent

Conditions

Temperature
0 °C

Procedure

The compound of Example 1 (c) (0.500 g, 0.922 mmol) was dissolved in anhydrous ether (10 ml) and diethylzinc (1.0M solution in hexanes, 1.84 ml, 1.84 mmol) was added. The solution was cooled to 0° C. and diiodomethane (0.15 ml 1.84 mmol) was added. The reaction was diluted with ethyl acetate (50 ml) and washed with saturated aqueous ammonium chloride solution. The organic layer was dried over (MgSO4) and evaporated. The residue was purified by chromatography on silica eluting with 5% ethyl acetate/hexanes→10% ethyl acetate/hexanes. The product obtained was left standing in HCl/ether for 16 h. The solvent was removed in vacuo and the title compound suspended in ether and filtered. 1H NMR (DMSO-d6) δ 7.90 (1H, s), 7.50 (2H, s), 7.29-7.40 (5H, m), 3.36 (2H, s), 3.17 (2H, m), 2.74 (2H, m), 2.30 (2H, m), 2.01 (2H, m), 1.13 (4H, m). MS (Cl+) 444 [M+H]+.

Workup

  1. washwashed with saturated aqueous ammonium chloride solution
  2. dry with materialThe organic layer was dried over (MgSO4)
  3. customevaporated
  4. customThe residue was purified by chromatography on silica eluting with 5% ethyl acetate/hexanes
  5. customThe product obtained
  6. waitwas left
  7. customThe solvent was removed in vacuo
  8. filtrationfiltered

Sources & evidence

ORD record
ord-ae3b656c0c7849aca4223139c73b343d
Source dataset
uspto-grants-1998_06
Patent number
US05760018

Linked notes

Loading…