Citric Acid → Methyl E-alpha-{2-(1-[4-chlorophenyl]-3-pyrazolyloxy)phenyl}-beta-methoxyacrylate

HRID 1421389Notes

Reaction equation

HRID 1421389 reaction equation
CC(C)([O-])C.[K+].[Br-].[CH3:8][O:9][CH2:10][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]2[CH:41]=[CH:40][C:39]([O:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3[C:49](=O)[C:50]([O:52][CH3:53])=[O:51])=[N:38]2)=[CH:33][CH:32]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]2[CH:41]=[CH:40][C:39]([O:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3/[C:49](=[CH:8]\[O:9][CH3:10])/[C:50]([O:52][CH3:53])=[O:51])=[N:38]2)=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 2773654(Methoxymethyl)triphenylphosphonium bromideHCID 15376176HCID 15376176, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 70293397Methyl E-alpha-{2-(1-[4-chlorophenyl]-3-pyrazolyloxy)phenyl}-beta-methoxyacrylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 0.38 g of potassium tert-butoxide in 3 ml of tetrahydrofuran was added dropwise at not more than 5° C to a suspension of 1.4 g of methoxymethyltriphenylphosphonium bromide ("Wittig reagent") in 15 ml of anhydrous tetrahydrofuran. 1.0 g of methyl 2-[1-(4-chlorophenyl)-3-pyrazolyloxy]phenylglyoxalate (cf. Ex. 1) in 5 ml of tetrahydrofuran was added to the dark red suspension, and the batch was allowed to come to room temperature. Wittig reagent was metered in twice more until all of the keto ester had reacted. For working-up, the batch was stirred into 20% by weight of aqueous citric acid and the mixture was extracted three times with methyl tert-butyl ether. The combined organic phases were washed until neutral, dried over sodium sulfate and subsequently concentrated. The crude product (3.2 g) was chromatographed over silica gel (eluent: toluene/ethyl acetate, 95/5). The resulting E/Z mixture was separated by medium-pressure chromatography on silica gel (eluent heptane/ethyl acetate, 9/1→7/3). This gave 0.5 g of the title compound and 0.15 g of the Z isomer.

Workup

  1. customto come to room temperature
  2. customhad reacted
  3. extractionthe mixture was extracted three times with methyl tert-butyl ether
  4. washThe combined organic phases were washed until neutral,
  5. dry with materialdried over sodium sulfate
  6. concentrationsubsequently concentrated
  7. customThe crude product (3.2 g) was chromatographed over silica gel (eluent: toluene/ethyl acetate, 95/5)
  8. customThe resulting E/Z mixture was separated by medium-pressure chromatography on silica gel (eluent heptane/ethyl acetate, 9/1→7/3)

Sources & evidence

ORD record
ord-10c7d319190a406cacc92c1b3b1a29b0
Source dataset
uspto-grants-2000_06
Patent number
US06075149

Reaction notes

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