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

HRID 1943293Notes

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-a3cb476fc4eb4d00920afc8b58b1863e
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08389743B2

Reaction notes

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