Chloroacetic Acid → HCID 70050009, compound

HRID 1389159Notes

Reaction equation

HRID 1389159 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Cl:17][CH2:18][C:19]([OH:21])=[O:20].Cl>CN(C=O)C.C(O)(C)C>[ClH:17].[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH2:18][C:19]([OH:21])=[O:20])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 300Chloroacetic AcidHCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 784611-Benzylpiperidin-4-ol

Product 1

HCID 70050009HCID 70050009, compoundYield 20.1%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent3×

Procedure

1-Benzyl-4-hydroxypiperidine (10 g) in dry DMF (50 ml) was added dropwise to a stirred suspension of sodium hydride (5 g, 50% dispersion in mineral oil) in dry DMF (50 ml) at 20° under an atmosphere of nitrogen. The suspension was stirred at 20° for 4 hours, then 2-chloroacetic acid (4.95 g) in DMF (50 ml) was added slowly in two equal portions with a 2 hour interval between each. The resulting thick slurry was stirred at 20° for 24 hours. Isopropanol (75 ml) was added and the slurry was acidified to pH 6 with 2 N hydrochloric acid then concentrated in vacuo. The aqueous residue was adjusted to pH 10 with sodium hydroxide solution and extracted with chloroform (3×100 ml). The aqueous layer was separated, acidified to pH 3 with 2 N hydrochloric acid and extracted with chloroform (3×100 ml). The organic extracts were again discarded and the aqueous phase was concentrated to half volume, filtered and the filtrate evaporated in vacuo to give 2-(1-benzylpiperidin-4-oxy)acetic acid, hydrochloride (3 g), characterised by n.m.r.

Workup

  1. stirringThe resulting thick slurry was stirred at 20° for 24 hours
  2. concentrationthen concentrated in vacuo
  3. extractionextracted with chloroform (3×100 ml)
  4. customThe aqueous layer was separated
  5. extractionextracted with chloroform (3×100 ml)
  6. concentrationthe aqueous phase was concentrated to half volume
  7. filtrationfiltered
  8. customthe filtrate evaporated in vacuo

Sources & evidence

ORD record
ord-3ee3862810ca4dccab73685c621a689c
Source dataset
uspto-grants-1981_01
Patent number
US04243666

Reaction notes

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