Hydrochloric Acid → (R)-1-[4-(3-Fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methoxy-methyl-amide

HRID 273183Notes

Reaction equation

HRID 273183 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:17](=[O:18])[CH2:16][C@@H:15]([C:19]([OH:21])=O)[CH2:14]2)=[CH:9][CH:8]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:38][NH:39][O:40][CH3:41].N1C=CC=CC=1.Cl>CN(C)C=O.O>[CH3:41][O:40][N:39]([CH3:38])[C:19]([C@@H:15]1[CH2:16][C:17](=[O:18])[N:13]([C:10]2[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]3[CH:22]=[CH:23][CH:24]=[C:2]([F:1])[CH:3]=3)=[CH:12][CH:11]=2)[CH2:14]1)=[O:21]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 67411567(R)-1-(4-((3-Fluorobenzyl)oxy)phenyl)-5-oxopyrrolidine-3-carboxylic acid

Product 1

HCID 86602842(R)-1-[4-(3-Fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methoxy-methyl-amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(R)-1-[4-(3-Fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (0.200 g, 0.001 mol) was dissolved in dry N,N-dimethylformamide (1 ml) under argon and the solution cooled to 0° C. 1,1′-Carbonyl-diimidazole (0.108 g, 0.001 mol) was added to the mixture and the reaction stirred for one hour while the temperature rose from 0° C. to room temperature. After the addition of N,O-dimethylhydroxylamine hydrochloride (0.063 g, 0.001 mol) and pyridine (0.053 ml, 0.001 mmol), the reaction was stirred for two hours at room temperature. Water (10 ml) and hydrochloric acid (0.1 N) was added and the mixture extracted with ethyl acetate. The organic phase was washed with a solution of sodium carbonate (1 M) and extracted again with ethyl acetate to yield 0.225 g (99% of theory). The crude product obtained in this way was used in the next step without further purification. MS: m/e=373.4(M+H)+.

Workup

  1. customrose from 0° C. to room temperature
  2. stirringthe reaction was stirred for two hours at room temperature
  3. extractionthe mixture extracted with ethyl acetate
  4. washThe organic phase was washed with a solution of sodium carbonate (1 M)
  5. extractionextracted again with ethyl acetate
  6. customto yield 0.225 g (99% of theory)

Sources & evidence

ORD record
ord-23967c69b9e64c34a86240d921d80b73
Source dataset
uspto-grants-2008_11
Patent number
US07456210B2

Reaction notes

Loading…