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

HRID 1501927Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

tert-Butyl(3S)-3-(hydroxymethyl)-4-[2-hydroxy-2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazine-1-carboxylate (3.3 g, 8.4 mmol) and cyanomethylene tri-n-butylphosphorane (3.65 g, 15.1 mmol) were dissolved in 30 mL of benzene, the solution was degassed, and then heated to 100° C. for 3 h. LC-MS showed the product peak (M+1=389). The reaction mixture was cooled and evaporated to dryness. The residue was purified by MPLC through a 330 g Redi-sep column and eluted with a 15% acetone/85% hexane mixture to yield a cis-trans mixture of the title compound.

Workup

customthe solution was degassed
temperatureThe reaction mixture was cooled
customevaporated to dryness
customThe residue was purified by MPLC through a 330 g Redi-sep column
washeluted with a 15% acetone/85% hexane mixture
customto yield

Sources & evidence

ORD record: ord-1c7398e683d74368b727eefb309abaff
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206199B2

Reaction notes

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