Acetonitrile → 1-Piperidinecarboxylic acid, 4-(acetylamino)-2-[(4-chlorophenyl)methyl]-, methyl ester, trans-

HRID 1738916Notes

Reaction equation

HRID 1738916 reaction equation
ClS(O)(=O)=O.[CH3:6][O:7][C:8](=[O:26])[N:9]([CH:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)[CH2:15][CH:16]=[CH2:17])[CH2:10]OCC.[OH-].[Na+].C(=O)([O-])[OH:30].[Na+].[C:34](#[N:36])[CH3:35]>>[CH3:6][O:7][C:8]([N:9]1[CH2:10][CH2:17][C@H:16]([NH:36][C:34](=[O:30])[CH3:35])[CH2:15][C@H:14]1[CH2:18][C:19]1[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=1)=[O:26]

Participants

6

Reactant 5

HCID 6342Acetonitrile2×HCID 14798Sodium HydroxideHCID 24638Chlorosulfonic acidHCID 516892Sodium BicarbonateHCID 53744314HCID 53744314, compound

Product 1

HCID 544394991-Piperidinecarboxylic acid, 4-(acetylamino)-2-[(4-chlorophenyl)methyl]-, methyl ester, trans-

Procedure

At -40° C., 20.6 ml (308 mmol) of chlorosulfonic acid are introduced into 500 ml of acetonitrile. A solution of 48.0 g (154 mmol) of N-[1-(4-chloro-benzyl)-but-3-enyl]-N-ethoxymethyl-carbamic acid methyl ester in 50 ml of acetonitrile is added dropwise in such a manner that the reaction temperature does not exceed -10° C. The mixture is then stirred for 20 minutes at -15° C. before 370 ml of 2 N sodium hydroxide solution and 100 ml of 10% aqueous sodium hydrogen carbonate solution are added to the reaction. The phases are separated and the aqueous phase is then extracted twice with toluene. The combined organic phases are dried over sodium sulfate. The crude product is crystallised from toluene and yields the title compound in the form of white crystals. M.p.: 169-170° C. TLC: methylene chloride/methanol/conc. ammonia (90:9:1) Rf =0.42, FD-MS: M+ =325.

Workup

  1. customdoes not exceed -10° C
  2. additionare added to the reaction
  3. customThe phases are separated
  4. extractionthe aqueous phase is then extracted twice with toluene
  5. dry with materialThe combined organic phases are dried over sodium sulfate
  6. customThe crude product is crystallised from toluene

Sources & evidence

ORD record
ord-bfa1b3300e0f4481a92fa0b4e9380c97
Source dataset
uspto-grants-1999_10
Patent number
US05965562

Reaction notes

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