Hydrochloric Acid → (2S,3S)-1-(3-Chloro-4-cyano-2-methylphenylcarbamoyl)-3-hydroxy-pyrrolidine-2-carboxylic acid

HRID 501596Notes

Reaction equation

HRID 501596 reaction equation
C[O:2][C:3]([C@@H:5]1[C@@H:9]([OH:10])[CH2:8][CH2:7][N:6]1[C:11](=[O:23])[NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[C:15]([Cl:21])[C:14]=1[CH3:22])=[O:4].Cl>[OH-].[Na+]>[Cl:21][C:15]1[C:14]([CH3:22])=[C:13]([NH:12][C:11]([N:6]2[CH2:7][CH2:8][C@H:9]([OH:10])[C@H:5]2[C:3]([OH:4])=[O:2])=[O:23])[CH:18]=[CH:17][C:16]=1[C:19]#[N:20]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 59754269(2S,3S)-1-(3-Chloro-4-cyano-2-methylphenylcarbamoyl)-3-hydroxy-pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 59754294(2S,3S)-1-(3-Chloro-4-cyano-2-methylphenylcarbamoyl)-3-hydroxy-pyrrolidine-2-carboxylic acidYield 104.3%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

A suspension of ester 54A (260 mg, 0.770 mmol) in 20 mL of 1.6 N NaOH was stirred at rt for 45 min. The reaction mixture was acidified to pH 2 with 10% HCl and extracted with EtOAc (3×). The combined organic layers were dried (MgSO4), filtered and the filtrate concentrated under reduced pressure to afford the title compound (260 mg) as a beige solid. A portion (50 mg) of the residue was purified by preparative HPLC (reverse phase silica gel, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA) to afford the title compound (25 mg) as a colorless oil. 1H NMR (CD3OD) 2.02-2.05 (m, 1H), 2.17-2.22 (m, 1H), 2.35 (s, 3H), 3.73-3.76 (m, 2H), 4.40 (br s, 1H), 4.49 (br s, 1H), 7.47 (d, J=8.80, 1H), 7.58 (d, J=8.25, 1H); 13C NMR (CD3OD) 15.83, 33.59, 45.61, 69.53, 74.73, 110.40, 117.45, 125.45, 132.34, 137.80, 144.42, 156.50, 159.95, 173.94; HPLC a) column: Phenomenex ODS C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA; 1 min hold, 4 mL/min UV detection at 220 nm, 1.97 min retention time; HPLC b) column: Shimadzu Shim-Pack VP-ODS C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 1.79 min retention time (92%); HPLC c) column: Daicel Chiralcel OD 4.6×250 mm, Isocratic 25% isopropanol/hexanes, 30 min, 1 mL/min, UV detection at 220 nm, 6.96 min retention time (98%); MS (ES) m/z 324 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-441ac9b249dc4c0bbc15c870647a377e
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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