3-Oxocyclobutane-1-carboxylic acid → 3-(3-Chloro-4-((pyrrolidin-1-yl)methyl)phenyl)-3-hydroxycyclobutanecarboxylic acid

HRID 1694428Notes

Reaction equation

[Li]CCCC.Br[C:7]1[CH:18]=[CH:17][C:10]([CH2:11][N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[C:9]([Cl:19])[CH:8]=1.[O:20]=[C:21]1[CH2:24][CH:23]([C:25]([OH:27])=[O:26])[CH2:22]1>C1COCC1>[Cl:19][C:9]1[CH:8]=[C:7]([C:21]2([OH:20])[CH2:24][CH:23]([C:25]([OH:27])=[O:26])[CH2:22]2)[CH:18]=[CH:17][C:10]=1[CH2:11][N:12]1[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

Conditions

Temperature: -78 °C

Procedure

A 2.5 M solution of n-BuLi in hexanes (60 ml, 150 mmol) was added over 15 min to a solution of intermediate 20, 1-(4-bromo-2-chlorobenzyl) pyrrolidine (41.2 g, 150 mmol) in THF (350 ml) under a flow of nitrogen at −78° C. The reaction mixture was stirred at −78° C. for 30 min. Then a −78° C., chilled solution of 3-oxocyclobutanecarboxylic acid (8.6 g, 75 mmol) in THF (100 ml) was added drop wise for 10 min at −78° C. The mixture was warmed to RT slowly and left stirring for 18 hrs and the resulting solution was used as an intermediate.

Workup

additionwas added drop wise for 10 min at −78° C
temperatureThe mixture was warmed to RT slowly
waitleft
stirringstirring for 18 hrs

Sources & evidence

ORD record: ord-775a232e141a4d7995f8954586315d82
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08158673B2

Reaction notes

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