Hydrochloric Acid → 2-(4-Benzyloxy-2,6-dichloro-benzyl)-2-(2,2-dimethoxy-ethyl)-malonic acid diethyl ester

HRID 1161767Notes

Reaction equation

HRID 1161767 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH:5]([CH2:11][CH:12]([O:15][CH3:16])[O:13][CH3:14])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[CH2:18]([O:25][C:26]1[CH:27]=[C:28]([Cl:35])[C:29]([CH2:33]Br)=[C:30]([Cl:32])[CH:31]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Cl>C1COCC1>[CH2:9]([O:8][C:6](=[O:7])[C:5]([CH2:33][C:29]1[C:28]([Cl:35])=[CH:27][C:26]([O:25][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:31][C:30]=1[Cl:32])([CH2:11][CH:12]([O:13][CH3:14])[O:15][CH3:16])[C:4]([O:3][CH2:1][CH3:2])=[O:17])[CH3:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14215238Diethyl (2,2-dimethoxyethyl)malonateHCID 592994282-Bromomethyl-1,3-dichloro-5-benzyloxy-benzene

Product 1

HCID 686483152-(4-Benzyloxy-2,6-dichloro-benzyl)-2-(2,2-dimethoxy-ethyl)-malonic acid diethyl esterYield 83.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Cool 2-(2,2-Dimethoxy-ethyl)-malonic acid diethyl ester (4.5 g, 16.3 mmol) in 50 mL THF to −78° C. and add lithium hexamethylsilane amide (1M, 17 mL) drop wise. After 15 min, add 5-benzyloxy-2-bromomethyl-1,3-dichloro-benzene (17.9 mmol 6.2 g) in 10 mL THF. Warm this mixture to ambient temperature, acidify with 1N HCl, and extract with ethyl acetate. Concentrate the organics and purify by normal phase column chromatography to afford the title compound as a white solid (7.0 g, 80%).

Workup

  1. extractionextract with ethyl acetate
  2. concentrationConcentrate the organics and
  3. custompurify by normal phase column chromatography

Sources & evidence

ORD record
ord-a666d68e49bb4753a72a92f0d2d38f37
Source dataset
uspto-grants-2010_10
Patent number
US07820659B2

Reaction notes

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