Methanol → 3-Cyano-3-(4-hydroxyphenyl)propanoic acid

HRID 922190Notes

Reaction equation

CO.C(OC(=O)[C:7](=[CH:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)[C:8]([O:10]CC)=[O:9])C.[C-:22]#[N:23].[K+]>O>[C:22]([CH:13]([C:14]1[CH:15]=[CH:16][C:17]([OH:20])=[CH:18][CH:19]=1)[CH2:7][C:8]([OH:10])=[O:9])#[N:23]

Participants

Conditions

Temperature: 70 °C

Procedure

To a 25 mL RB flask fitted with magnetic stirrer was charged with methanol (6 mL) and water (1 mL). To the stirred solvent was added 2-(4-hydroxy-benzylidene)-malonic acid diethyl ester (1 g, 3.8 mmol), followed by potassium cyanide (0.492 g, 7.6 mmol). The RM was heated at 70° C. for 2 h. The RM was concentrated, diluted with saturated NaHCO3 solution (50 mL) and washed with ethyl acetate (50 mL×2). The aqueous layer was acidified to pH 3 with 1N hydrochloric acid and extracted with ethyl acetate (50 mL×2). The organic layer was washed with water (50 mL) and saturated brine solution (50 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The product was obtained as brown liquid. (0.6 g, yield: 72.3%); MS (ESI, 120 eV): m/z=190.0 (M−H)+; 1H NMR (300 MHz, DMSO-d6): δ 12.69 (s, 1H), 9.58 (s, 1H), 7.22-7.24 (d, 2H), 6.75-6.78 (d, 2H), 4.28-4.40 (m, 1H), 2.77-3.12 (m, 2H).

Workup

customTo a 25 mL RB flask fitted with magnetic stirrer
concentrationThe RM was concentrated
additiondiluted with saturated NaHCO3 solution (50 mL)
washwashed with ethyl acetate (50 mL×2)
extractionextracted with ethyl acetate (50 mL×2)
washThe organic layer was washed with water (50 mL) and saturated brine solution (50 mL)
dry with materialThe organic layer was dried over anhydrous Na2SO4
customthe solvent was removed under reduced pressure
customThe product was obtained as brown liquid

Sources & evidence

ORD record: ord-59a9a04257e342729c542655394221d6
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278915B2

Reaction notes

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