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

HRID 570321Notes

Reaction equation

HRID 570321 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

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 352460Methyl 2-bromo-3-methoxypropanoateHCID 27828273,3-Difluoropyrrolidine

Product 1

HCID 712812272-(3,3-Difluoropyrrolidin-1-yl)-3-methoxypropanoic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

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

  1. customto afford a residue which
  2. customAll solvents were removed under vacuum

Sources & evidence

ORD record
ord-a5e09d88d38c468ea5828ae0f5375f94
Source dataset
uspto-grants-2015_05
Patent number
US09023839B2

Reaction notes

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