Ethyl bromoacetate → 2-({1-[(Tert-butoxy)carbonyl]piperidin-3-yl}methoxy)acetic acid

HRID 611608Notes

Reaction equation

[OH-].[Na+].S([O-])(O)(=O)=O.C([NH3+])CCC.[OH:13][CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1.Br[CH2:29][C:30]([O:32]CC)=[O:31]>C1(C)C=CC=CC=1>[C:30]([CH2:29][O:13][CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1)([OH:32])=[O:31]

Participants

Conditions

Temperature: 15 °C

Procedure

200 ml of 50% sodium hydroxide solution and 1 g of butylammonium hydrogen sulphate are added to a solution of 21.5 g of tert-butyl rac 3-hydroxymethyl-piperidine-1-carboxylate [K. Hilpert et al., J. Med. Chem., 37: 3889 (1994); EP 0 468 231] in 200 ml of toluene. The 2-phase mixture is cooled to 15° C. and treated with 30 ml of ethyl bromoacetate while stirring vigorously. After stirring at room temperature for 2.5 hours the reaction mixture is poured on to ice-water and extracted twice with ether. The organic phases are washed 4 times with water. The combined aqueous phases are acidified with concentrated hydrochloric acid and extracted twice with ethyl acetate. The ethyl acetate phases are washed with sodium chloride solution, dried and evaporated. There are obtained 18.3 g of tert-butyl rac-3-carboxymethoxymethyl-piperidine-1-carboxylate as a yellow oil, MS: 273 (M)+.

Workup

stirringAfter stirring at room temperature for 2.5 hours the reaction mixture
extractionextracted twice with ether
washThe organic phases are washed 4 times with water
extractionextracted twice with ethyl acetate
washThe ethyl acetate phases are washed with sodium chloride solution
customdried
customevaporated

Sources & evidence

ORD record: ord-519cf8335c8340b78d366e6d90f75ae9
Source dataset: uspto-grants-1999_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06001855

Reaction notes

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