Hydrochloric Acid → (3S,4R)-1-(tert-butoxycarbonyl)-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylic acid

HRID 1675851Notes

Reaction equation

HRID 1675851 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][C@H:10]2[C:21]([O:23]C)=[O:22])[CH:5]=[CH:6][C:7]=1[Cl:8].[Li+].[OH-].Cl>CO>[C:17]([O:16][C:14]([N:12]1[CH2:13][C@@H:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[C@H:10]([C:21]([OH:23])=[O:22])[CH2:11]1)=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 66618423(3S,4R)-1-tert-butyl 3-methyl 4-(3,4-dichlorophenyl)pyrrolidine-1,3-dicarboxylate

Product 1

HCID 51441165(3S,4R)-1-(tert-butoxycarbonyl)-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Boc anhydride (3.0 g, 13.7 mmol) was added to a solution of (3S,4R)-methyl 4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate (3.10 g, 11.3 mmol) in THF (100 mL) and TEA (4 mL) was added. The mix was stirred at room temperature overnight. The solvent was removed and the residue was subject to column chromatography, eluted by hexane/ethyl acetate (8:1) to give (3S,4R)-1-tert-butyl 3-methyl 4-(3,4-dichlorophenyl)pyrrolidine-1,3-dicarboxylate (LCMS (APCI+) [M-Boc+H]+ 274.1; Rt: 4.17 min.). The (3S,4R)-1-tert-butyl 3-methyl 4-(3,4-dichlorophenyl)pyrrolidine-1,3-dicarboxylate was re-dissolved in MeOH (50 mL), and LiOH (3M, 10 mL) was added. The mixture was stirred at room temperature for 6 hours. 2N HCl (15 mL) was added to the mixture. The solvent was removed, and the residue was subject to column chromatography, eluted by DCM/MeOH (40:1-10:1) to give (3S,4R)-1-(tert-butoxycarbonyl)-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylic acid (1.95 g). LCMS (APCI+) [M-Boc+H]+ 260.1; Rt: 3.67 min.

Workup

  1. customThe solvent was removed
  2. washeluted by DCM/MeOH (40:1-10:1)

Sources & evidence

ORD record
ord-efde0ad0ab3547d0ab5ed43b6ea5bbd3
Source dataset
uspto-grants-2011_08
Patent number
US08003651B2

Reaction notes

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