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

HRID 1943271Notes

Reaction equation

HRID 1943271 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-3b99562fa04c4b69b1543acca0e5c23f
Source dataset
uspto-grants-2013_03
Patent number
US08389743B2

Reaction notes

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