Chloromethyl Methyl Ether → 2-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one

HRID 1879557Notes

Reaction equation

HRID 1879557 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]3[C:22]([C:23](=[O:26])[C:24]=2[OH:25])=[CH:21][CH:20]=[C:19]([O:27][CH2:28][O:29][CH3:30])[CH:18]=3)=[CH:11][C:10]=1[O:31][CH2:32][O:33][CH3:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[CH2:45][O:46][CH3:47]>C(Cl)Cl.CCOCC>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]3[C:22]([C:23](=[O:26])[C:24]=2[O:25][CH2:45][O:46][CH3:47])=[CH:21][CH:20]=[C:19]([O:27][CH2:28][O:29][CH3:30])[CH:18]=3)=[CH:11][C:10]=1[O:31][CH2:32][O:33][CH3:34])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 669338322-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3-hydroxy-7-(methoxymethoxy)-4H-chromen-4-one

Product 1

HCID 669339302-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-oneYield 90.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To 2-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3-hydroxy-7-(methoxymethoxy)-4H-chromen-4-one (55 mg, 0.12 mmol) in 2 mL of DCM was added DIPEA (31 mg, 0.24 mmol), followed by slow addition of chloro(methoxy)methane (15 mg, 0.18 mmol). The reaction mixture was stirred at rt under Ar atmosphere for 3 h and diluted with ether (30 mL). It was washed with water (3×30 mL) and dried over MgSO4 and concentrated. The crude product was purified with silica chromatography (hexane/EtOAc) to afford 2-(4-(benzyloxy)-3-(methoxymethoxy)phenyl)-3,7-bis(methoxymethoxy)-4H-chromen-4-one as a white solid (55 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=8.8 hz, 1H), 7.91 (d, J=2.0 Hz, 1H), 7.71 (dd, J=8.4 Hz, 2.0 Hz, 1H), 7.46-7.44 (m, 2H), 7.39 (m, 2H), 7.34-7.31 (m, 1H), 7.12 (d, J=2.4 Hz, 1H), 7.05 (dd, J=8.8, 2.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 5.30 (s, 2H), 5.28 (s, 2H), 5.24 (s, 2H), 5.21 (s, 2H), 3.55 (s, 3H), 3.51 (s, 3H), 3.18 (s, 3H); MS (ESI) m/z 509 (M+H+).

Workup

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

Sources & evidence

ORD record
ord-a1635b1cfb694b158616e6ed5af316d8
Source dataset
uspto-grants-2012_11
Patent number
US08318132B2

Reaction notes

Loading…