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

HRID 559437Notes

Reaction equation

HRID 559437 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). The mixture 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 redissolved 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-3a19e58049194095ae3f4805a44541cb
Source dataset
uspto-grants-2011_11
Patent number
US08063050B2

Reaction notes

Loading…