Cesium carbonate → 4-(6-Methoxy-3-methyl-2-thiophen-3-yl-naphthalen-1-yloxy)-benzaldehyde

HRID 1992962Notes

Reaction equation

HRID 1992962 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][CH2:14]OC)=[C:8]([C:17]1[CH:21]=[CH:20][S:19][CH:18]=1)[C:7]([CH3:22])=[CH:6]2.C([O-])([O-])=O.[Cs+].[Cs+].FC1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[CH:32][CH:31]=1>Cl.O1CCOCC1.O.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[CH:32][CH:31]=1)=[C:8]([C:17]1[CH:21]=[CH:20][S:19][CH:18]=1)[C:7]([CH3:22])=[CH:6]2

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 680234-FluorobenzaldehydeHCID 685377683-(6-Methoxy-1-(methoxymethoxy)-3-methyl-naphthalen-2-yl)-thiophene

Product 1

HCID 860871844-(6-Methoxy-3-methyl-2-thiophen-3-yl-naphthalen-1-yloxy)-benzaldehydeYield 74%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

A solution of 3-(6-Methoxy-1-methoxymethoxy-3-methyl-naphthalen-2-yl)-thiophene (199) (0.347 g, 1.10 mmol) in 4 N HCl/Dioxane (5 mL) was stirred at room temperature for 30 min. The solvent was removed from the reaction mixture, then dissolved in DMSO (3 mL) followed by addition of Cs2CO3 (0.899 g, 2.76 mmol) and 4-fluorobenzaldehye (0.142 mL, 1.32 mmol). The reaction mixture was irradiated with microwave at 80° C. for 4.5 h. Reaction mixture was diluted with water and EtOAc, separated the layers, then the aqueous layer was extracted with EtOAc. The combined organic layer was washed with water followed by brine, dried over Na2SO4, filtered and concentrated. The crude material was purified with a gradient of 5% EtOAc in hexanes over 50 min to afford 0.304 g (74%) of the title compound (200) as oil. 1H NMR (400 MHz, d-CDCl3): δ 2.32 (s, 3H), 3.93 (s, 3H), 6.74 (d, J=8.6 Hz, 2H), 6.90-6.91 (m, 1H), 7.02-7.06 (m, 2H), 7.13 (m, 1H), 7.20-7.22 (m, 1H), 7.58 (s, 1H), 7.65 (d, J=8.7 Hz, 2H), 7.69 (d, J=9.2 Hz, 1H), 9.81 (s, 1H).

Workup

  1. customThe solvent was removed from the reaction mixture
  2. dissolutiondissolved in DMSO (3 mL)
  3. customThe reaction mixture was irradiated with microwave at 80° C. for 4.5 h
  4. customReaction mixture
  5. customseparated the layers
  6. extractionthe aqueous layer was extracted with EtOAc
  7. washThe combined organic layer was washed with water
  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 50 min

Sources & evidence

ORD record
ord-821b33bd811f4374b4bef6037272625c
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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