Water → (3-(2-(3-Chlorophenyl)ethyl)-2-pyridinyl)(1-methyl-4-piperidinyl)methanone hydrochloride

HRID 1606946Notes

Reaction equation

HRID 1606946 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[C:11]([C:16]#N)=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:18][N:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[Mg]Cl.[OH2:27]>C1COCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[C:11]([C:16]([CH:22]3[CH2:23][CH2:24][N:19]([CH3:18])[CH2:20][CH2:21]3)=[O:27])=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 41232253-(2-(3-Chlorophenyl)ethyl)-2-pyridinecarbonitrileHCID 178480302HCID 178480302, compound

Product 1

HCID 13920590(3-(2-(3-Chlorophenyl)ethyl)-2-pyridinyl)(1-methyl-4-piperidinyl)methanone hydrochlorideYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of compound 3-[2-(3-chlorophenyl) ethyl]-2-pyridinecarbonitrile (118 g; 0.49 mol) in 1.2 L of dry THF was added 395 mL (2.48 N; 0.59 mol) of N-methyl-piperidyl magnesium chloride over 0.5 h while the temperature was maintained at 40°-50° C. by cooling with water as necessary. The reaction mixture was maintained at 40°-50° C. for an additional 0.5 h. The reaction was quenched to below pH 2 by the addition of 2N hydrochloric acid and the resulting solution was stirred at 25°-30° C. for 1 h. The bulk of the THF was removed by distillation and the pH of the solution adjusted to 3.5 by the addition of aqueous sodium hydroxide. The mixture was cooled to 5° C. and the product was collected by filtration, washed with cold water and dried under vacuum at 60° C. to give 168 g (91%) of [3-[2-(3-chlorophenyl) ethyl]-2-pyridinyl]-1-methyl-4-piperidinyl methanone hydrochloride as a crystalline solid: mp 183°-185° C.; NMR (200 MHz, DMSO)δ2.72 (s,3H), 2.8-2.9 (m,2H) 3.0-3.2 (m,4H), 3.3-3.5 (m,3H), 3.9-4.1 (m, 1H), 7.2-7.3 (m,1H), 7.3-7.4 (m,3H), 7.57 (dd,1H,J=6, 4Hz), 7.84 (dd,1H, J=6, 1.2 Hz), 8.59 (dd,1H,J=4, 1.2 Hz), 10.95 (br s, 1H); mass spectrum m/e (rel intensity) 345M+2 (32), 343M+ (100). Anal. Calcd for C20H24N2OCl2 : C,63.32; H,6.38; N,7.39; Cl,18.69. Found: C,63.45; H,6.47; N,7.40; Cl, 18.49.

Workup

  1. temperaturewas maintained at 40°-50° C.
  2. temperatureThe reaction mixture was maintained at 40°-50° C. for an additional 0.5 h
  3. customThe reaction was quenched to below pH 2 by the addition of 2N hydrochloric acid
  4. customThe bulk of the THF was removed by distillation
  5. additionthe pH of the solution adjusted to 3.5 by the addition of aqueous sodium hydroxide
  6. filtrationthe product was collected by filtration
  7. washwashed with cold water
  8. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-7c4eea1836d54226b452cae25c3f61d7
Source dataset
uspto-grants-1989_09
Patent number
US04863931

Reaction notes

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