Diisopropylethylamine → 2-(diallylamino)-N-(3,5-difluoro-4-(trimethyisilyl)phenyl)-2-(4-(methoxymethyl)phenyl)acetamide

HRID 2202333Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:13])[C:8]=1[Si:9]([CH3:12])([CH3:11])[CH3:10])[NH2:5].[CH2:14]([N:17]([CH2:31][CH:32]=[CH2:33])[CH:18]([C:22]1[CH:27]=[CH:26][C:25]([CH2:28][O:29][CH3:30])=[CH:24][CH:23]=1)[C:19](O)=[O:20])[CH:15]=[CH2:16].CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[CH2:31]([N:17]([CH2:14][CH:15]=[CH2:16])[CH:18]([C:22]1[CH:23]=[CH:24][C:25]([CH2:28][O:29][CH3:30])=[CH:26][CH:27]=1)[C:19]([NH:5][C:4]1[CH:6]=[C:7]([F:13])[C:8]([Si:9]([CH3:10])([CH3:12])[CH3:11])=[C:2]([F:1])[CH:3]=1)=[O:20])[CH:32]=[CH2:33]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 3,5-difluoro-4-(trimethylsilyl)aniline (5 g, 24.84 mmol), 2-(diallylamino)-2-(4-(methoxymethyl)phenyl)acetic acid (8.21 g, 29.81 mmol), DMAP (3.34 g, 27.32 mmol) and DIEA (21.69 mL, 124.20 mmol) in ethyl acetate (150 mL) was added T3P (29.2 mL, 49.68 mmol), and the mixture was stirred at 80° C. for 2 hr. To the reaction mixture were added water and ethyl acetate, and the organic layer was separated. The organic layer was washed with water and brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane) to give 2-(diallylamino)-N-(3,5-difluoro-4-(trimethylsilyl)phenyl)-2-(4-(methoxymethyl)phenyl)acetamide (6.79 g, 14.81 mmol, 59.6%) as a pale-yellow oil. This compound was used for the next step without further purification.

Workup

customthe organic layer was separated
washThe organic layer was washed with water and brine
dry with materialdried over magnesium sulfate
customthe solvent was evaporated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-57d7261555f24884b47e370376b581af
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365520B2

Reaction notes

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