N-((1S)-1-(4-Bromophenyl)ethyl)acetamide → (S)-N-(1-{4-[3-(tert-Butyl-dimethyl-silanyloxy)-azetidin-1-yl]-phenyl}-ethyl)-acetamide

HRID 40499Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11](=[O:13])[CH3:12])[CH3:9])=[CH:4][CH:3]=1.[C:14]([Si:18]([CH3:25])([CH3:24])[O:19][CH:20]1[CH2:23][NH:22][CH2:21]1)([CH3:17])([CH3:16])[CH3:15].CC([O-])(C)C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>O1CCOCC1.CO.O>[C:14]([Si:18]([CH3:25])([CH3:24])[O:19][CH:20]1[CH2:23][N:22]([C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][C:11](=[O:13])[CH3:12])[CH3:9])=[CH:4][CH:3]=2)[CH2:21]1)([CH3:17])([CH3:16])[CH3:15]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 3.0 g (12.4 mmol) (S)—N-[1-(4-bromo-phenyl)-ethyl]-acetamide (I.1), 2.3 g (12.4 mmol) 3-(tert-butyl-dimethyl-silanyloxy)-azetidine (US2008/214520A1), 4.9 g (97%, 49.6 mmol) NaOtBu, 1.48 g (4.96 mmol) 2-(di-tert-butylphosphino)biphenyl and 1.1 g (1.24 mmol) tris-(dibenzylideneacetone)-dipalladium(0) in 30 mL 1,4-dioxane is stirred for 45 min under microwave irradiation at 80° C. After cooling water and MeOH are added, the mixture is filtered, concentrated in vacuo and directly purified by HPLC (column: XbridgeC18; eluent A: water+0.3% NH4OH, eluent B: MeOH) to yield the desired product.

Workup

additionare added
filtrationthe mixture is filtered
concentrationconcentrated in vacuo
customdirectly purified by HPLC (column: XbridgeC18; eluent A: water+0.3% NH4OH, eluent B: MeOH)

Sources & evidence

ORD record: ord-dcd68dc0bcee42018476560e3ed1afa3
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530461B2

Reaction notes

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