4-Methoxybenzyl alcohol → (1-Hydroxy-5-methoxy-3-methyl-naphthalen-2-yl)-(4-methoxy-benzyloxy)-acetic acid ethyl ester

HRID 514037Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:21]([O:23][C:24](=[O:41])[CH:25]=[C:26]1[CH:35]([CH3:36])[CH:34](Br)[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][C:32]=2[O:38][CH3:39])[C:27]1=[O:40])[CH3:22]>C1COCC1>[CH2:21]([O:23][C:24](=[O:41])[CH:25]([C:26]1[C:35]([CH3:36])=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][C:32]=2[O:38][CH3:39])[C:27]=1[OH:40])[O:8][CH2:7][C:6]1[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[CH3:22]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-methoxybenzyl alcohol (0.27 mL, 4 equiv) in THF (11 mL) at 0° C. was added KHMDS (0.5 M in toluene, 3.4 mL, 3 equiv) and the resulting mixture was allowed to stir for 10 min at 0° C. A solution of (4-bromo-5-methoxy-3-methyl-1-oxo-3,4-dihydro-1H-naphthalen-2-ylidene)-acetic acid ethyl ester (200 mg) in THF (1 mL) was added slowly. After stirring for 3 min at 0° C., the reaction was quenched with citric acid (1 M) and extracted with EtOAc. The organic extracts were washed with brine, dried over Na2SO4 and concentrated. The crude residue was purified by flash column chromatography (5-20% EtOAc/hexanes) to give 157 mg of pale orange oil (68% yield). LCMS-ESI+ (m/z): [M+H]+ calcd for C24H27O6: 411.18. Found: 411.21.

Workup

stirringAfter stirring for 3 min at 0° C.
customthe reaction was quenched with citric acid (1 M)
extractionextracted with EtOAc
washThe organic extracts were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated
customThe crude residue was purified by flash column chromatography (5-20% EtOAc/hexanes)

Sources & evidence

ORD record: ord-903d7234fedb4984bb35bce9ab864c09
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102614B2

Reaction notes

Loading…