Dimethoxymethane → 1-(4-Chlorobenzyl)-3-methoxymethoxymethyl-3-methyl-2-oxocyclopentane carboxylic acid methyl ester

HRID 1752013Notes

Reaction equation

HRID 1752013 reaction equation
[CH3:1][O:2][C:3]([C:5]1([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:9][CH2:8][C:7]([CH3:12])([CH2:10][OH:11])[C:6]1=[O:13])=[O:4].[CH3:22][O:23][CH2:24]OC.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O>C(Cl)Cl.[Cl-].[Na+].O>[CH3:1][O:2][C:3]([C:5]1([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=2)[CH2:9][CH2:8][C:7]([CH2:10][O:11][CH2:22][O:23][CH3:24])([CH3:12])[C:6]1=[O:13])=[O:4]

Participants

6

Reactant 3

HCID 8020DimethoxymethaneHCID 14812Phosphorus oxide (P4O10)HCID 672540121-(4-Chlorobenzyl)-3-hydroxymethyl-3-methyl-2-oxocyclopentanecarboxylic acid methyl ester2×

Product 1

HCID 672579561-(4-Chlorobenzyl)-3-methoxymethoxymethyl-3-methyl-2-oxocyclopentane carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

1-(4-Chlorobenzyl)-3-methyl-3-hydroxymethyl-2-oxocyclopentane carboxylic acid methyl ester (Compound (XI), R1=CH3, R2=CH3, Ym=4-Cl) (186 mg, 0.60 mmol) was dissolved in methylene chloride (5.6 ml), and dimethoxymethane (2.8 ml) was added. This was cooled in a water bath, diphosphorus pentoxide (372 mg) was added and vigorous stirring was conducted at room temperature for 10 minutes. After completion of the reaction, saturated brine was combined with the reaction solution, and extraction with diethyl ether was conducted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate. The solvent was distilled away and dried under reduced pressure to obtain a crude 1-(4-chlorobenzyl)-3-methoxymethoxymethyl-3-methyl-2-oxocyclopentane carboxylic acid methyl ester (Compound (X), R1=CH3, R2=CH3, Ym=4-Cl, G=CH2OCH2OCH3) (195 mg). From this, an aliquot (188.8 mg) was dissolved in isopropanol (0.53 ml), a 2M aqueous solution of sodium hydroxide (0.53 ml, 1.12 mmol) was added, and stirring was conducted at 60 degrees C. for 1 hour. After completion of the reaction, water was added and extraction with ethyl acetate was conducted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate. The solvent was distilled away, and the residue was purified by silica gel column chromatography (eluent; hexane:ethyl acetate=7:1) to obtain the desired substance as a mixture of two isomers (Isomer (a):Isomer (b)=36:65).

Workup

  1. temperatureThis was cooled in a water bath
  2. extractionwas combined with the reaction solution, and extraction with diethyl ether
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled away
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-3e39343dbc794064bdb76b6974f82247
Source dataset
uspto-grants-2015_10
Patent number
US09162966B2

Reaction notes

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