tert-butyl (3S)-3-(hydroxymethyl)piperazine-1-carboxylate → tert-butyl(3S)-3-(hydroxymethyl)-4-[2-hydroxy-2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazine-1-carboxylate

HRID 1501926Notes

Reaction equation

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

Participants

Conditions

Temperature: 150 °C

Procedure

5-(Oxiran-2-yl)-2-benzofuran-1(3H)-one (1.5 g, 8.5 mmol) and commercially available (S)-4-N—BOC-2-hydroxymethyl piperazine (2.394 g, 11.07 mmol) were combined in ethanol (10 mL) in a microwave tube. The mixture was degassed then heated for 60 min at 150° C. LC-MS showed the product peak. The reaction was worked up by adding ethyl acetate and washing once with brine. The organic layer was separated, dried, and concentrated to dryness. The crude product was purified by MPLC using an 80 g Redi-sep column and eluted with 50%-100% EtOAc/hexane yielding the title compound.

Workup

customThe mixture was degassed
additionby adding ethyl acetate
washwashing once with brine
customThe organic layer was separated
customdried
concentrationconcentrated to dryness
customThe crude product was purified by MPLC
washeluted with 50%-100% EtOAc/hexane yielding the title compound

Sources & evidence

ORD record: ord-46dab300aa3e4aba998386750e6c0722
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206199B2

Reaction notes

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