3-Oxocyclobutane-1-carboxylic acid → 3-(3-Fluoro-4-(pyrrolidin-1-ylmethyl)phenyl)-3-hydroxycyclobutanecarboxylic acid

HRID 1694408Notes

Reaction equation

HRID 1694408 reaction equation
C([Li])CCC.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]([F:19])[CH:8]=1.[O:20]=[C:21]1[CH2:24][CH:23]([C:25]([OH:27])=[O:26])[CH2:22]1>C1COCC1>[F: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

5

Reactant 3

HCID 49133583-Oxocyclobutane-1-carboxylic acidHCID 222667231-(4-Bromo-2-fluorobenzyl)pyrrolidineHCID 178418339Butyllithium

Product 1

HCID 672787123-(3-Fluoro-4-(pyrrolidin-1-ylmethyl)phenyl)-3-hydroxycyclobutanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (2.5M/hexanes, 78 ml, 0.195 mol) was added down the reaction flask walls over 5 min to a −78° C. solution of 1-(4-bromo-2-fluorobenzyl)pyrrolidine (50.0 g, 0.194 mol) in THF (500 mL). After stirring at −78° C. for 1 h, a −78° C. solution of 3-oxocyclobutanecarboxylic acid (11.0 g, 96.4 mmol) in THF (150 mL) was cannulated over 10 min into the reaction mixture. The resulting dark orange solution was slowly warmed to room temperature over 16 h. LC/MS of the mixture showed the title compound 294.2 (M+H). This material was used as a crude solution without work-up, assuming ˜0.12 M concentration of the title compound.

Sources & evidence

ORD record
ord-7e980f48b27340ab8fd7d86e994bdec8
Source dataset
uspto-grants-2012_04
Patent number
US08158673B2

Reaction notes

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