Dimethyl Sulfoxide → 4-Fluoro-2,3-dihydro-7-methoxy-1-methylene-1H-indene

HRID 1492956Notes

Reaction equation

[H-].[Na+].[F:3][C:4]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]2[C:5]=1[CH2:6][CH2:7][C:8]2=O.[CH3:16]S(C)=O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:3][C:4]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]2[C:5]=1[CH2:6][CH2:7][C:8]2=[CH2:16]

Participants

Conditions

Temperature: 80 °C

Procedure

NaH (6.8 g) suspended in dimethyl sulfoxide (40 ml) under nitrogen is heated to 80° C. for 1 h. A further 40 ml dimethyl sulfoxide and then 80 g of methyltriphenylphosphonium bromide is added in portions. After stirring for 15 min, 20 g III, partially suspended in 40 ml dimethylsulfoxide, is added and the mixture heated to 70° C. overnight. Pouring the mixture onto ice + hexane followed by extraction with hexane gives 17.6 g of crude 4-fluoro-7-methoxy-1-methyleneindan (IV) which was dissolved in 70 ml MeOH. This solution is added to a stirred solution of the trihydrate of thallium trinitrate (43.9 g) in 400 ml of MeOH and HC(OCH3)3. After stirring for 1 min, 200 ml chloroform is added at once. Washing with aqueous sodium bicarbonate, drying and concentrating gives a crude product which is purified by chromatography (silica, diethyl ether-hexane 1:1). The resulting mixture of V and its dimethylketal is hydrolyzed with 1 M HCl-diethyl ether to give 11.8 g V. 1H NMR (chloroform-d1) δ 7.02-6.64 (m, 2H); 3.79 (s, 3H); 3.51 (s, 2H); 3.10 (t, 2H); 2.56 (t, 2H).

Workup

additionis added
temperaturethe mixture heated to 70° C. overnight
additionPouring the mixture onto ice + hexane
extractionfollowed by extraction with hexane

Sources & evidence

ORD record: ord-9b44aed36c4a455c80a55b7ffe82e1e8
Source dataset: uspto-grants-1994_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05376687

Reaction notes

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