Potassium Carbonate → Bepotastine Ethyl Ester

HRID 381667Notes

Reaction equation

HRID 381667 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[O:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.Br[CH2:23][CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[O:9][CH:10]2[CH2:11][CH2:12][N:13]([CH2:23][CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:14][CH2:15]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrateHCID 108920052-((4-Chlorophenyl)(piperidin-4-yloxy)methyl)pyridine, (S)-

Product 1

HCID 15055867Bepotastine Ethyl EsterYield 93.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

In 15 ml of acetone was dissolved 1.33 g (4.39 mmol, optical purity: 99.4% e.e.) of (S)-(−)-4-[(4-chlorophenyl) (2-pyridyl)methoxy]piperidine obtained according to Reference example 1, then, 1.03 g (5.28 mmol) of ethyl 4-bromobutanoate and 0.73 g (5.28 mmol) of potassium carbonate were added, and the mixture was refluxed under stirring for 7 hours. Insolubles were filtered off and the filtrate was concentrated under reduced pressure. The resulting slightly yellowish oily product was purified by silica gel column chromatography using a mixed solvent of chloroform and methanol (volume ratio: 30:1) as an eluent. Fractions containing the isolated objective compound were concentrated under reduced pressure to afford 1.71 g of ethyl (S)-4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]-butanoate as an oily product (Yield: 93.4%, optical purity: 99.4% e.e.). [α]D25 −6.60° (c=1, MeOH)

Workup

  1. customobtained
  2. temperaturethe mixture was refluxed
  3. filtrationInsolubles were filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe resulting slightly yellowish oily product was purified by silica gel column chromatography
  6. additionFractions containing the isolated objective compound
  7. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-093f01e184024c81a88ea7988267991a
Source dataset
uspto-grants-2001_10
Patent number
US06307052B1

Reaction notes

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