3,5-Dimethoxybenzaldehyde → [3-(Tert-butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-(3,5-dimethoxyphenyl)-methanol

HRID 970958Notes

Reaction equation

HRID 970958 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:16][CH3:17])=[C:6]([CH:15]=1)[O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].C([Li])CCC.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([O:33][CH3:34])[CH:32]=1)[CH:28]=[O:29]>>[C:11]([Si:8]([CH3:10])([CH3:9])[O:7][C:6]1[CH:15]=[C:2]([CH:28]([C:27]2[CH:30]=[C:31]([O:33][CH3:34])[CH:32]=[C:25]([O:24][CH3:23])[CH:26]=2)[OH:29])[CH:3]=[CH:4][C:5]=1[O:16][CH3:17])([CH3:14])([CH3:13])[CH3:12]

Participants

4

Reactant 3

HCID 817473,5-DimethoxybenzaldehydeHCID 109800492-(T-Butyldimethylsilyloxy)-4-bromoanisoleHCID 178418339Butyllithium

Product 1

HCID 69204033[3-(Tert-butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-(3,5-dimethoxyphenyl)-methanolYield 69.5%

Procedure

(5-Bromo-2-methoxyphenoxy)-tert-butyldimethylsilane (0.98 g, 3.09 mmol), n-butyl lithium (1.24 ml, 3.09 mmol), and 3,5-dimethoxybenzaldehyde (0.47 g, 2.81 mmol) were treated in the same manner as described above for the synthesis of (2,3-drihydrobenzo[1,4]dioxin-6-yl)-(3,5-dimethoxyphenyl)methanol. The crude material was purified via flash column chromatography (5% EtOAc in hexane gradient to 30% EtOAc in hexane in about 40 min.) to give [3-(tert-butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-(3,5-dimethoxy-phenyl)-methanol as an oil (0.79 g, 69%), HPLC purity was 98.3% at 2.55 min. (90/10 ACN/0.1% H3PO4): 1HNMR (CDCl3) δ 6.92-6.78 (m, 3H, Ar), 6.53 (d, J=2 Hz, 2H, Ar), 6.35 (t, J=2 Hz, 1H, Ar), 5.66 (d, J=3 Hz, 1H, CH), 3.78 (s, 3H, single OCH3), 3.76 (s, 6H, 2OCH3), 2.15 (d, J=3 Hz, 1H, OH), 0.97 (s, 9H, 3OCH3), 0.13 (s, 6H, 2OCH3). The product was carried over to the next step.

Workup

  1. customThe crude material was purified via flash column chromatography (5% EtOAc in hexane gradient to 30% EtOAc in hexane in about 40 min.)

Sources & evidence

ORD record
ord-055c2532a8b14236ba87cc6b8e301b9e
Source dataset
uspto-grants-2007_12
Patent number
US07312241B2

Reaction notes

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