L-Hydroxyproline → (2S,3R)-1-(3-Chloro-4-cyano-2-methylphenylcarbamoyl)-3-hydroxypyrrolidine-2-carboxylic acid methyl ester

HRID 751085Notes

Reaction equation

HRID 751085 reaction equation
N1C[C@H](O)C[C@H]1C(O)=O.[CH3:10][O:11][C:12]([C@@H:14]1[C@H:18]([OH:19])[CH2:17][CH2:16][NH:15]1)=[O:13].[Cl:20][C:21]1[C:28]([CH3:29])=[C:27]([N:30]=[C:31]=[O:32])[CH:26]=[CH:25][C:22]=1[C:23]#[N:24]>C(Cl)Cl>[CH3:10][O:11][C:12]([C@@H:14]1[C@H:18]([OH:19])[CH2:17][CH2:16][N:15]1[C:31](=[O:32])[NH:30][C:27]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[C:21]([Cl:20])[C:28]=1[CH3:29])=[O:13]

Participants

5

Reactant 3

HCID 5810L-HydroxyprolineHCID 167318492-Chloro-4-isocyanato-3-methylbenzonitrileHCID 45082777Methyl (3R)-3-hydroxy-L-prolinate

Product 1

HCID 59754287(2S,3R)-1-(3-Chloro-4-cyano-2-methylphenylcarbamoyl)-3-hydroxypyrrolidine-2-carboxylic acid methyl esterYield 67.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of hydroxyproline compound 1F (493 mg, 3.40 mmol) in CH2Cl2 (15 mL) was added 4 Å molecular sieves (˜3.0 g), followed by isocyanate 23E (725 mg, 3.22 mmol), and the resulting mixture was stirred at rt overnight, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, 0.5% MeOH in EtOAc/hexane, 1:1) to afford the title compound (736 mg) as an off-white solid. HPLC column: YMC S-5 C18 (4.6×50 mm), 0% to 100% B, 4 min gradient, 1 min hold (A=90% H2O—10% CH3CN—0.1% TFA and B=10% H2O—90% CH3CN—0.1% TFA), flow rate at 4 mL/min, UV detection at 220 nm, 1.57 min retention time (100%); MS (ES) m/z 338 [M+H]+.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by flash chromatography (silica gel, 0.5% MeOH in EtOAc/hexane, 1:1)

Sources & evidence

ORD record
ord-9fae3f099d41493e81f5fa4c3904c5f0
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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