Trimethylsilylacetylene → 8-[(Cyclopropyl-methyl-amino)-methyl]-2,2,4,4-tetramethyl-6-trimethylsilanylethynyl chroman

HRID 1869840Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH2:12][N:13]([CH:16]3[CH2:18][CH2:17]3)[CH:14]=O)[CH:11]=1)[O:8][C:7]([CH3:20])([CH3:19])[CH2:6][C:5]2([CH3:22])[CH3:21].[CH3:23][Si:24]([C:27]#[CH:28])([CH3:26])[CH3:25]>C(N(CC)CC)C.O1CCCC1.C(OCC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:16]1([N:13]([CH2:12][C:10]2[CH:11]=[C:2]([C:28]#[C:27][Si:24]([CH3:26])([CH3:25])[CH3:23])[CH:3]=[C:4]3[C:9]=2[O:8][C:7]([CH3:20])([CH3:19])[CH2:6][C:5]3([CH3:22])[CH3:21])[CH3:14])[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 6-bromo-8-[(cyclopropyl-formyl-amino)-methyl]-2,2,4,4-tetramethyl-chroman (Intermediate 9, 1.5 g, 4.2 mmol) in triethyl amine (5 mL) and anhydrous tetrahydrofuran (10 mL) was treated with copper(I)iodide (0.32 g, 1.68 mmol) and sparged with argon for 5 minutes. Trimethylsilyl acetylene (2.5 mL, 17.6 mmol) was then added followed by dichlorobis(triphenylphosphine)palladium(II) (0.737 g, 1.05 mmol). The resulting reaction mixture was heated at 70° C. for 17 h. It was then cooled to ambient temperature, diluted with diethyl ether and filtered over a bed of celite. The filtrate was evaporated vacuo to an oil which was subjected to flash column chromatography over silica gel (230-400 mesh) to afford the title compound as a brown oil.

Workup

customsparged with argon for 5 minutes
customThe resulting reaction mixture
temperatureIt was then cooled to ambient temperature
filtrationfiltered over a bed of celite
customThe filtrate was evaporated vacuo to an oil which

Sources & evidence

ORD record: ord-3fe81f4573944380a714cb558ebf6332
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07638648B2

Reaction notes

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