(3S)-3-hydroxypyrrolidin-2-one → (S)-1-(7-Fluoro-3-oxo-indan-5-yl)-3-hydroxy-pyrrolidin-2-one

HRID 533922Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C:8]2=[O:11])=[C:4]([F:12])[CH:3]=1.[OH:13][C@H:14]1[CH2:18][CH2:17][NH:16][C:15]1=[O:19]>O1CCOCC1>[F:12][C:4]1[CH:3]=[C:2]([N:16]2[CH2:17][CH2:18][C@H:14]([OH:13])[C:15]2=[O:19])[CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][C:8]2=[O:11]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-bromo-4-fluoro-indan-1-one (Enamine, 453 mg), (S)-3-hydroxy-pyrrolidin-2-one (200 mg) and 1,4-dioxane (3 mL) was purged with argon. Cesium carbonate (645 mg), N,N′-dimethyl-ethylene-diamine (2.24 mL) and copper(I) iodide (38 mg) were added and the mixture was heated to 80° C. for 3 hours. After cooling to r.t. the mixture was filtered and the filtrate evaporated. The residue was purified by SGC (eluent: heptane/EA 1:1 with 0 to 20% MeOH) to provide the title compound. MS ESI+: m/z=250 [M+H]+.

Workup

customwas purged with argon
additionCesium carbonate (645 mg), N,N′-dimethyl-ethylene-diamine (2.24 mL) and copper(I) iodide (38 mg) were added
temperatureAfter cooling to r.t. the mixture
filtrationwas filtered
customthe filtrate evaporated
customThe residue was purified by SGC (eluent: heptane/EA 1:1 with 0 to 20% MeOH)

Sources & evidence

ORD record: ord-1b1e47d73419402a9150a66e95dae664
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853412B2

Reaction notes

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