Phenylacetic Acid → HCID 21676188, compound

HRID 2220824Notes

Reaction equation

HRID 2220824 reaction equation
[C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:11]([C:13]1[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][C:14]=1O)[CH3:12].N1CC[O:25][CH2:24]C1.C(OCC)(OCC)OCC>B(F)(F)F.CCOCC>[CH3:12][O:11][C:13]1[C:18]([O:19][CH3:20])=[C:17]2[C:16]([C:24](=[O:25])[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:8][O:10]2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 999Phenylacetic AcidHCID 8083MorpholineHCID 31214Ethyl orthoformateHCID 788282,3-Dimethoxyphenol

Product 1

HCID 21676188HCID 21676188, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 8000Boron trifluoride etherateSolvent

Conditions

Temperature
80 °C

Procedure

This compound was prepared as described in the synthesis of analog 23. A mixture of 2.76 g of phenylacetic acid (20.08 mmol), 5.0 g of 2, 3-dimethoxylphenol (32.43 mmol) and 50 ml of boron trifluoride diethyl ether ate was stirred at 80° C. for 19 hours. Reaction mixture was then cooled to RT and washed with aqueous K2CO3 and water sequentially until pH of the filtrate approached neutrality. Product was extracted with ethyl acetate and concentrated to dryness. The residue, which contained mostly 2-hydroxy-3,4-dimethoxyphenylbenzylketone, was dissolved in 50 ml of 2-propanol and 3.0 ml of morpho line and 6.0 ml of triethyl orthoformate (36.07 mmol) were added. The mixture was stirred at 80° C. for 20 hours and evaporated to dryness. The residue was fractionated on a silica gel (chloroform-methanol system) and fractions that contained pure product were pooled, dried, and recrystallized from acetone to give 300 mg of analog 34 (crystalline plates), a yield of 6% (based on 2,3-dimethoxylphenol, w/w): mp 143-144° C. 1HNMR (DMSO-d6) δ 3.89 (8-OCH3), 3.96 (7-OCH3), 7.30 (d, 1H, J=9.03, Hz, 6-H), 7.39 (t, 1H, J=6.94 Hz, 4′-H), 7.43 (t, 2H, J=7.06, 7.72 Hz, 3′, 5′-H), 7.57 (dd, 2H, J=7.26, 1.44 Hz, 2′, 6′-H), 7.87 (d, 1H, J=8.88 Hz, 5-H), 8.50 (s, 1H, 2H). 13C NMR (DMSO-d6) δ 56.5 (—OCH3), 60.9 (—OCH3), 111.0 (C-6), 118.5 (C-10), 120.9 (C-3), 123.3 (C-1′), 127.8 (C-5), 128.1 (C-3′, 5′), 128.9 (C-2′, 6′), 131.9 (C-4′), 136.1(C-8), 149.9(C-7), 154.1 (C-2), 156.2 (C-9), 174.6 (C-4). MS (m/z) 283.3 (M+H)+, 305.4 (M+Na)+, 281.9 (M−H)−. Anal. (C17H14O4) for C, H. Cacld: 72.33, 4.99; found: 72.21, 4.97.

Workup

  1. customThis compound was prepared
  2. customas described in the synthesis of analog 23
  3. customReaction mixture
  4. temperaturewas then cooled to RT
  5. washwashed with aqueous K2CO3 and water sequentially until pH of the filtrate
  6. extractionProduct was extracted with ethyl acetate
  7. concentrationconcentrated to dryness
  8. dissolutionwas dissolved in 50 ml of 2-propanol
  9. stirringThe mixture was stirred at 80° C. for 20 hours
  10. customevaporated to dryness
  11. customdried
  12. customrecrystallized from acetone
  13. customto give 300 mg of analog 34 (crystalline plates)

Sources & evidence

ORD record
ord-6bbbdada2aef421d976db3a99dd3265b
Source dataset
uspto-grants-2008_05
Patent number
US07368434B2

Reaction notes

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