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

HRID 1943277Notes

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 (101 mL, 254 mmol) was added over 15 min to a solution of 1-(4-bromo-2-chlorobenzyl)pyrrolidine (69.6 g, 254 mmol) in absolute THF (450 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 (14.4 g, 126.7 mmol) in absolute THF (150 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. LRMS m/z Calcd for C16H20NClO3, 309.8, found, 308.1 (M−H) APCI.

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-746a97e343234af7a5d8e8762e215507
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08389743B2

Reaction notes

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