Acetone cardice → 3-[4-(6-Methoxy-3-methyl-2-thiophen-3-yl-naphthalen-1-yloxy)-phenyl]-acrylic acid ethyl ester

HRID 1992963Notes

Reaction equation

HRID 1992963 reaction equation
[Li][CH2:2][CH2:3][CH2:4][CH3:5].[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[C:14]([O:18][C:19]1[CH:26]=[CH:25]C(C=O)=[CH:21][CH:20]=1)=[C:13]([C:27]1[CH:31]=[CH:30][S:29][CH:28]=1)[C:12]([CH3:32])=[CH:11]2.[CH3:33][C:34](C)=[O:35].C(=O)=[O:38]>C1COCC1>[CH2:34]([O:35][C:2](=[O:38])[CH:3]=[CH:4][C:5]1[CH:25]=[CH:26][C:19]([O:18][C:14]2[C:15]3[C:10](=[CH:9][C:8]([O:7][CH3:6])=[CH:17][CH:16]=3)[CH:11]=[C:12]([CH3:32])[C:13]=2[C:27]2[CH:31]=[CH:30][S:29][CH:28]=2)=[CH:20][CH:21]=1)[CH3:33]

Participants

5

Reactant 3

HCID 18522661Acetone cardiceHCID 860871844-(6-Methoxy-3-methyl-2-thiophen-3-yl-naphthalen-1-yloxy)-benzaldehydeHCID 178418339Butyllithium

Product 1

HCID 685397883-[4-(6-Methoxy-3-methyl-2-thiophen-3-yl-naphthalen-1-yloxy)-phenyl]-acrylic acid ethyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of triethylphosphonoacetate (0.242 mL, 1.22 mmol) in dry THF (4 mL) at −78° C. was slowly added 1.6 M nBuLi (0.812 mL, 1.30 mmol) then stirred for 30 min at above temperature. 4-(6-Methoxy-3-methyl-2-thiophen-3-yl-naphthalen-1-yloxy)-benzaldehyde (200) (0.304 g, 0.812 mmol) in dry THF (4 mL) was added to the reaction mixture slowly then stirred reaction mixture at above temperature for 1 h. The reaction was taken out of the acetone-dry ice bath and stirred at room temperature for 3 h. The reaction was quenched with 1 N HCl and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The crude material was purified with a gradient of 5% EtOAc in hexanes over 60 min to afford 0.27 g (75%) of compound (201) as a yellow solid. 1H NMR (400 MHz, d-CDCl3): δ 1.28-1.32 (t, J=7.1, 7.2 Hz, 3H), 2.31 (s, 3H), 3.92 (s, 3H), 4.20-4.25 (m, 2H), 6.23 (d, J=15.9 Hz, 1H), 6.62 (d, J=8.8 Hz, 2H), 6.90-6.91 (m, 1H), 7.01-7.02 (m, 2H), 7.04-7.05 (m, 1H), 7.11-7.12 (m, 1H), 7.20-7.22 (m, 1H), 7.28 (d, J=8.8 Hz, 1H), 7.53-7.57 (m, 2H), 7.72 (d, J=9.2 Hz, 1H).

Workup

  1. customat −78° C.
  2. stirringstirred
  3. customreaction mixture at above temperature for 1 h
  4. stirringstirred at room temperature for 3 h
  5. customThe reaction was quenched with 1 N HCl
  6. extractionextracted with EtOAc
  7. washThe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified with a gradient of 5% EtOAc in hexanes over 60 min

Sources & evidence

ORD record
ord-d962cd1e521448ea846a9c2ed2ccca90
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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