Acetaldehyde → 1-Ethyl-4-[1-(phenylmethoxycarbonyl)-4-piperidinyl]piperidine

HRID 1782720

Reaction equation

HRID 1782720 reaction equation
[C:1]1([CH2:7][O:8][C:9]([N:11]2[CH2:16][CH2:15][CH:14]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH2:13][CH2:12]2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([BH3-])#N.[Na+].[CH3:27][C:28]1C=C(C2(C3C=C(Br)C(O)=C(C)C=3)OS(=O)(=O)C3C2=CC=CC=3)C=C(Br)C=1O.C(=O)C>CO.O.CO.Cl>[CH2:27]([N:20]1[CH2:21][CH2:22][CH:17]([CH:14]2[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[O:10])[CH2:12][CH2:13]2)[CH2:18][CH2:19]1)[CH3:28]

Participants

8

Reactant 4

HCID 177AcetaldehydeHCID 8273Bromocresol PurpleHCID 5003444Sodium cyanoborohydrideHCID 10979576N-Cbz-4,4'-bipiperidine

Product 1

HCID 183212841-Ethyl-4-[1-(phenylmethoxycarbonyl)-4-piperidinyl]piperidine

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a solution of 18.14 g (0.061 mol) of 1-(phenylmethoxycarbonyl)-4-(4-piperidinyl)piperidine in 450 ml of a methanol/water mixture (1/1 v/v) were added, with stirring, whilst maintaining a temperature of 15 to 20° C., 10.05 g (0.152 mol) of 95% sodium cyanoborohydride and 50 mg of bromocresol purple. Then a solution of 10.57 g (0.24 mol) of acetaldehyde in 50 ml of methanol and 1N hydrochloric acid were alternately added dropwise so that the colour of the mixture changed continuously from blue to yellow. After all had been added and the reaction had finished the mixture was adjusted to pH 2 with hydrochloric acid and extracted twice with 200 ml of diethylether. The aqueous phase was then made alkaline and extracted thoroughly with dichloromethane. The combined dichloromethane extracts were dried over magnesium sulphate and evaporated down in vacuo. The colourless crystallising residue remaining was purified by column chromatography over silica gel (30-60 μm) using FM1 as eluant. Yield of colourless crystals of melting point 93-96° C.: 7.9 g (39.2% of theory).

Workup

  1. additionAfter all had been added
  2. extractionextracted twice with 200 ml of diethylether
  3. extractionextracted thoroughly with dichloromethane
  4. dry with materialThe combined dichloromethane extracts were dried over magnesium sulphate
  5. customevaporated down in vacuo
  6. customThe colourless crystallising residue remaining was purified by column chromatography over silica gel (30-60 μm)

Sources & evidence

ORD record
ord-7067cbc152254b86b5c05ae99b72eb8b
Source dataset
uspto-grants-2009_03
Patent number
US07498325B2

Linked notes

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