Potassium Carbonate → [2S,3S]-1-(4-chlorobut-2-yn-1-yl)-2-phenyl-3-[3-(1-methyl-1H-[1,2,3]triazol-5-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine

HRID 355377Notes

Reaction equation

HRID 355377 reaction equation
Cl.[C:2]1([C@H:8]2[C@@H:13]([O:14][CH2:15][C:16]3[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]4[N:30]([CH3:31])[N:29]=[N:28][CH:27]=4)[CH:17]=3)[CH2:12][CH2:11][CH2:10][NH:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:32][CH2:33][C:34]#[C:35][CH2:36]Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:32][CH2:33][C:34]#[C:35][CH2:36][N:9]1[CH2:10][CH2:11][CH2:12][C@H:13]([O:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[C:18]([C:26]3[N:30]([CH3:31])[N:29]=[N:28][CH:27]=3)[CH:17]=2)[C@@H:8]1[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 131821,4-Dichloro-2-butyneHCID 67717432[2S,3S]-2-phenyl-3-[3-(1-methyl-1H-[1,2,3]triazol-5-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine hydrochloride

Product 1

HCID 18666489[2S,3S]-1-(4-chlorobut-2-yn-1-yl)-2-phenyl-3-[3-(1-methyl-1H-[1,2,3]triazol-5-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of [2S,3S]-2-phenyl-3-[3-(1-methyl-1H-[1,2,3]triazol-5-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine hydrochloride (270 mg) in N,N-dimethylformamide (3.0 ml) was slowly added to a solution of 1,4-dichlorobut-2-yne (189 ml) and potassium carbonate (269 mg) in N,N-dimethylformamide (5.0 ml). The solution was stirred for 18 hours at room temperature and the solvent removed under reduced pressure. To the residue was added water (40 ml) and the product was extracted with ethyl acetate (3×10 ml). The combined organic fractions were washed with water, saturated brine, dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue was purified by MPLC (40% ethyl acetate/hexane) to give [2S,3S]-1-(4-chlorobut-2-yn-1-yl)-2-phenyl-3-[3-(1-methyl-1H-[1,2,3]triazol-5-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine as a yellow oil (142 mg). 1H NMR (360 MHz,CDCl3) δ 1.52 (2H, m), 2.16 (2H, m), 2.64 (1H, m), 3.00 (1H, m), 3.30 (2H, m), 3.48 (1H, br s), 3.57 (1H, s), 3.98 (3H, s), 4.11 (1H, d, J=11.0 Hz), 4.15 (1H, s) 4.52 (2H, d, J=11.0 Hz), 7.17-7.26 (4H, m), 7.40-7.47 (4H, m), 7.68 (1H, s).

Workup

  1. customthe solvent removed under reduced pressure
  2. additionTo the residue was added water (40 ml)
  3. extractionthe product was extracted with ethyl acetate (3×10 ml)
  4. washThe combined organic fractions were washed with water, saturated brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. customThe residue was purified by MPLC (40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4a997508a061401fbb38d96999d089d7
Source dataset
uspto-grants-1998_11
Patent number
US05830892

Reaction notes

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