Hydrochloric Acid → 2-(3,3-Difluoropyrrolidin-1-yl)-3-methoxypropanoic acid

HRID 405804

Reaction equation

Br[CH:2]([CH2:7][O:8][CH3:9])[C:3]([O:5]C)=[O:4].[F:10][C:11]1([F:16])[CH2:15][CH2:14][NH:13][CH2:12]1.C([O-])([O-])=O.[K+].[K+].[Li+].[OH-].Cl>CN(C=O)C.C1COCC1.CO.O>[F:10][C:11]1([F:16])[CH2:15][CH2:14][N:13]([CH:2]([CH2:7][O:8][CH3:9])[C:3]([OH:5])=[O:4])[CH2:12]1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of methyl 2-bromo-3-methoxypropanoate (132.0 mg, 0.66 mmol), 3,3-difluoropyrrolidine (70.6 mg, 0.66 mmol) and K2CO3 (91.2 mg, 0.66 mmol) in DMF (2 mL) was heated at 90° C. for 3 hours. The mixture was subjected to standard aqueous workup to afford a residue which was dissolved in THF/MeOH/H2O (3:2:1, 5 mL). LiOH (6N, 3.3 mmol) was added and the resulting mixture was stirred at room temperature for 30 minutes. The solution was acidified to pH5 by addition of 6N HCl. All solvents were removed under vacuum to give a crude 2-(3,3-difluoropyrrolidin-1-yl)-3-methoxypropanoic acid (58) which was used without purification. MS m/z 210.1 (M+1)+.

Workup

customto afford a residue which
customAll solvents were removed under vacuum

Sources & evidence

ORD record: ord-410d96b87ba142b4925751567c93760b
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754071B2

Linked notes

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