Acetic Anhydride → (E)-3-(4-fluoro-3-methoxyphenyl)-2-(4-isopropoxyphenyl)acrylic acid

HRID 1852089

Reaction equation

HRID 1852089 reaction equation
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=[O:13])=[CH:7][CH:6]=1)([CH3:3])[CH3:2].[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][C:17]=1[O:24][CH3:25].CC(OC(C)=O)=O.CCN(CC)CC>O.CCOC(C)=O>[F:15][C:16]1[CH:23]=[CH:22][C:19](/[CH:20]=[C:11](\[C:8]2[CH:9]=[CH:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:6][CH:7]=2)/[C:12]([OH:14])=[O:13])=[CH:18][C:17]=1[O:24][CH3:25]

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 799528Benzeneacetic acid, 4-(1-methylethoxy)-HCID 27373584-Fluoro-3-methoxybenzaldehyde

Product 1

HCID 70978345(E)-3-(4-fluoro-3-methoxyphenyl)-2-(4-isopropoxyphenyl)acrylic acidYield 65.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(4-isopropoxyphenyl)acetic acid (3.97 g, 20.44 mmol), 4-fluoro-3-methoxybenzaldehyde (3.15 g, 20.44 mmol), Ac2O (3.47 ml, 36.8 mmol), and Et3N (1.994 ml, 14.31 mmol) were heated to 110° C. for 16 h. The reaction was cooled down to rt and diluted with water and EtOAc. The organic layer was collected, dried over sodium sulfate, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 10-20% EtOAc/Hexanes. The product fractions were collected and the solvent removed under vacuum to give (E)-3-(4-fluoro-3-methoxyphenyl)-2-(4-isopropoxyphenyl)acrylic acid (4.4 g, 65% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.85 (s, 1H), 7.22-7.16 (m, 2H), 6.98-6.91 (m, 3H), 6.82 (ddd, J=8.3, 4.6, 2.1 Hz, 1H), 6.63 (dd, J=8.5, 2.0 Hz, 1H), 4.64-4.54 (m, 1H), 3.51 (s, 3H), 1.39-1.35 (m, 6H).

Workup

  1. customThe organic layer was collected
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe crude material was purified by silica gel chromatography
  5. customThe product fractions were collected
  6. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-d37ddf9b5f3b47e8bf8a9e7e164026ea
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Linked notes

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