Cesium fluoride → [8-(3-Methoxyphenyl)-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl]phosphonic acid diethyl ester

HRID 48335Notes

Reaction equation

[CH2:1]([O:3][P:4]([CH:9]=[C:10]1[NH:16][CH2:15][CH2:14][N:13]([CH3:17])[C:12]2[CH:18]=[C:19](Br)[CH:20]=[CH:21][C:11]1=2)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[CH3:23][O:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1.[F-].[Cs+]>O1CCOCC1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH2:1]([O:3][P:4]([CH:9]=[C:10]1[NH:16][CH2:15][CH2:14][N:13]([CH3:17])[C:12]2[CH:18]=[C:19]([C:29]3[CH:28]=[CH:27][CH:26]=[C:25]([O:24][CH3:23])[CH:30]=3)[CH:20]=[CH:21][C:11]1=2)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To 300 mg (0.77 mmol) of (8-bromo-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl)phosphonic acid diethyl ester (prepared as described in Example 41) in 1 ml of dioxane was added 123 mg (0.81 mmol) of 3-methoxyphenylboronic acid, 7.8 mg (0.028 mmol) of tricyclohexylphosphine, 10.5 mg 0.012 mmol) of tris-(dibenzylideneacetone)-palladium (0) and 141 mg of caesium fluoride. The mixture was heated at 80° C. for 6 hours. The mixture was partitioned between ethyl acetate and water. The organic phase was evaporated and the product was purified by column chromatography (20 g IST pre-packed column) eluting with acetone—petroleum ether (40-60° C.) (1:2) to give 217 mg of [8-(3-methoxyphenyl)-1-methyl-1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-ylidenemethyl]phosphonic acid diethyl ester as a yellow gum; MS: m/e 417 (M+).

Workup

customThe mixture was partitioned between ethyl acetate and water
customThe organic phase was evaporated
customthe product was purified by column chromatography (20 g IST pre-packed column)
washeluting with acetone—petroleum ether (40-60° C.) (1:2)

Sources & evidence

ORD record: ord-4b8a9d83c10b49f9a95dc9ddb26de91e
Source dataset: uspto-grants-2004_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06703387B2

Reaction notes

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