4-Methoxybenzoic Acid → p-methoxybenzoyl-L-prolinal dimethyl acetal

HRID 467149Notes

Reaction equation

HRID 467149 reaction equation
[C:1]([OH:11])(=O)[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C(P(C#N)(CC)=O)C.C([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])C.[CH:27]1C=CC=CC=1.[C:33]([O:36][CH2:37]C)(=[O:35])C>CN(C)C=O>[CH3:27][O:35][CH:33]([O:36][CH3:37])[C@@H:25]1[CH2:26][CH2:24][CH2:23][N:22]1[C:1](=[O:11])[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 74784-Methoxybenzoic AcidHCID 8471TriethylamineHCID 13586794DiethylphosphorylcyanideHCID 21583983Benzene ethyl acetate

Product 1

HCID 15132638p-methoxybenzoyl-L-prolinal dimethyl acetalYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butoxycarbonyl-L-prolinal dimethyl acetal (1.0 g, 4.08 mmol) is stirred for one hour at room temperature in 10% HCl-methanol (8.2 ml) and the mixture is evaporated to dryness under reduced pressure to give quantitatively L-prolinal dimethylacetal hydrochloride as a solid. The product is dissolved in dimethylformamide (5 ml) containing p-anisic acid (938 mg, 6.16 mmol) and diethyl-phosphoryl cyanide (0.65 ml, 8.25 mmol). To the solution is added dropwise triethylamine (1.15 ml, 8.25 mmol) under cooling and agitation in an ice-methanol bath. After the dropwise addition the mixture is stirred for one hour under cooling and then for one hour at room temperature. Benzene-ethyl acetate (2:1, 150 ml) is added to the reaction mixture and the organic layer was separated, washed successively with a saturated aqueous solution of sodium hydrogen carbonate (15 ml), water (15 ml) and a saturated aqueous solution of edible salt (15 ml), dried over sodium sulfate and filtered. The filtrate is concentrated to dryness under reduced pressure. The residue is purified by column chromatography on silica gel (n-hexane-dichloromethanemethanol, 6:4:1) to give 747 mg (65%) of the title compound as white crystals.

Workup

  1. temperatureunder cooling
  2. additionAfter the dropwise addition the mixture
  3. temperatureunder cooling
  4. waitfor one hour at room temperature
  5. customthe organic layer was separated
  6. washwashed successively with a saturated aqueous solution of sodium hydrogen carbonate (15 ml), water (15 ml)
  7. dry with materiala saturated aqueous solution of edible salt (15 ml), dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated to dryness under reduced pressure
  10. customThe residue is purified by column chromatography on silica gel (n-hexane-dichloromethanemethanol, 6:4:1)

Sources & evidence

ORD record
ord-784059b961f242cf92fa0aec34b6e2e1
Source dataset
uspto-grants-1992_10
Patent number
US05158970

Reaction notes

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