Cyanomethylenetributylphosphorane → tert-butyl(9aS)-3-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

HRID 2175771Notes

Reaction equation

O[CH2:2][C@H:3]1[N:8]([CH2:9][CH:10]([OH:22])[C:11]2[CH:20]=[CH:19][C:14]3[C:15](=[O:18])[O:16][CH2:17][C:13]=3[C:12]=2[CH3:21])[CH2:7][CH2:6][N:5]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:4]1.C(C=P(CCCC)(CCCC)CCCC)#N>C1C=CC=CC=1>[CH3:21][C:12]1[C:13]2[CH2:17][O:16][C:15](=[O:18])[C:14]=2[CH:19]=[CH:20][C:11]=1[CH:10]1[O:22][CH2:2][C@@H:3]2[CH2:4][N:5]([C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])[CH2:6][CH2:7][N:8]2[CH2:9]1

Participants

Conditions

Temperature: 100 °C

Procedure

tert-Butyl(3S)-3-(hydroxymethyl)-4-[2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazine-1-carboxylate (3.3 g, 8.2 mmol) and cyanomethylene tri-n-butylphosphorane (2 equivalents) were dissolved in 45 mL benzene in a sealed and degassed tube. The mixture was heated to 100° C. for 3 h. The reaction mixture was cooled and evaporated to dryness. The residue was purified by chromatography through a 330 g Redi-sep column and eluted with 30% acetone/70% hexane mixture to yield the title compound as a cis-trans mixture. LC-MS: M+1=389.

Workup

customa sealed
customdegassed tube
temperatureThe reaction mixture was cooled
customevaporated to dryness
customThe residue was purified by chromatography through a 330 g Redi-sep column
washeluted with 30% acetone/70% hexane mixture

Sources & evidence

ORD record: ord-d34fcd97b49c4c8aab01011aea3bd9a6
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062070B2

Reaction notes

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