Cesium carbonate → 2-(4-(2-fluoroethoxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one

HRID 1879559Notes

Reaction equation

HRID 1879559 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:15]([C:16](=[O:22])[C:17]=2[O:18][CH2:19][O:20][CH3:21])=[CH:14][CH:13]=[C:12]([O:23][CH2:24][O:25][CH3:26])[CH:11]=3)=[CH:4][C:3]=1[O:27][CH2:28][O:29][CH3:30].Br[CH2:32][CH2:33][F:34].C([O-])([O-])=O.[Cs+].[Cs+]>CN1C(=O)CCC1.CCOCC>[F:34][CH2:33][CH2:32][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:15]([C:16](=[O:22])[C:17]=2[O:18][CH2:19][O:20][CH3:21])=[CH:14][CH:13]=[C:12]([O:23][CH2:24][O:25][CH3:26])[CH:11]=3)=[CH:4][C:3]=1[O:27][CH2:28][O:29][CH3:30]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 129822-Fluoroethyl bromideHCID 669340932-(4-hydroxy-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one

Product 1

HCID 866513762-(4-(2-fluoroethoxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-oneYield 85.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To 2-(4-hydroxy-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one (20 mg, 0.048 mmol) and 1-bromo-2-fluoroethane (18 mg, 0.14 mmol) in 0.3 mL NMP was added Cs2CO3 (39 mg, 0.12 mmol). The mixture was stirred at rt for 15 h under Ar atmosphere and diluted with ether (30 mL). It was washed with NaH2PO4 (sat. 30 mL) and water (2×30 mL) and dried over MgSO4 and concentrated. The crude product was purified with chromatography (hexane/EtOAc) to afford 2-(4-(2-fluoroethoxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one as a white solid (19 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J=8.8 Hz, 1H), 7.91 (d, J=2.0 Hz, 1H), 7.76 (dd, J=8.4 Hz, 2.0 Hz, 1H), 7.13 (d, J=2.4 Hz, 1H), 7.05 (dd, J=8.8, 2.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 5.29 (s, 4H), 5.22 (s, 2H), 4.89 (m, 1H), 4.78 (m, 1H), 4.40 (m. 1H), 4.32 (m, 1H), 3.56 (s, 3H), 3.51 (s, 3 H) 3.20 (s, 3H); MS (ESI) m/z 465 (M+H+).

Workup

  1. washIt was washed with NaH2PO4 (sat. 30 mL) and water (2×30 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe crude product was purified with chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-b73ecbad1388432b99ba8a7aec1e1521
Source dataset
uspto-grants-2012_11
Patent number
US08318132B2

Reaction notes

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