1,1'-Carbonyldiimidazole → (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide

HRID 1516624Notes

Reaction equation

HRID 1516624 reaction equation
C(N1C=CN=C1)([N:3]1C=CN=C1)=O.[F:13][C:14]1[CH:15]=[C:16]([CH:34]=[CH:35][CH:36]=1)[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[CH2:28][C@H:27]([C:31](O)=[O:32])[CH2:26]2)=[CH:21][CH:20]=1>O1CCCC1>[F:13][C:14]1[CH:15]=[C:16]([CH:34]=[CH:35][CH:36]=1)[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29](=[O:30])[CH2:28][C@H:27]([C:31]([NH2:3])=[O:32])[CH2:26]2)=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 67409315(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid

Product 1

HCID 44128415(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amideYield 96.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
18 °C

Procedure

1,1′-carbonyldiimidazole (8.27 g, 51.0 mmol) was suspended and partly dissolved in tetrahydrofuran (110 mL) at 18° C. (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (14.0 g, 42.5 mmol; enantiomeric purity (S):(R)=99.5:0.5) was added as a solid together with tetrahydrofuran (30 mL) used for rinsing. The turbid solution, which turned into a white suspension after 15 min, was stirred 1 h at 16-20° C. and then transferred into a stirred 25% aqueous ammonia solution (7.95 mL) in tetrahydrofuran (80 mL). The last part of the white suspension was transferred with the aid of tetrahydrofuran (10 mL) for rinsing. After stirring for 0.5 h the reaction mixture was concentrated in vacuo to a volume of ˜70 mL and diluted with water (300 mL). Some ice was added to keep the temperature at 20-25° C. The white precipitate was collected by filtration, washed with water/tetrahydrofuran 80:20 and with heptane. Drying in vacuo at 20-45° C. afforded (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide (13.5 g, 96%) as a white solid. The purity of the material by HPLC was 96.9% (area) and the enantiomeric ratio (S):(R) was determined as 99.7:0.3.

Workup

  1. washfor rinsing
  2. washfor rinsing
  3. stirringAfter stirring for 0.5 h the reaction mixture
  4. concentrationwas concentrated in vacuo to a volume of ˜70 mL
  5. additiondiluted with water (300 mL)
  6. additionSome ice was added
  7. customat 20-25° C
  8. filtrationThe white precipitate was collected by filtration
  9. washwashed with water/tetrahydrofuran 80:20 and with heptane
  10. customDrying in vacuo at 20-45° C.

Sources & evidence

ORD record
ord-cdbd61a6a0ad400e92a51b2194a13bf3
Source dataset
uspto-grants-2012_07
Patent number
US08227505B2

Reaction notes

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