Methanesulfonic Acid → (S)-3-[4-(3-fluorobenzyloxy) benzylamino]pyrrolidin-2-one

HRID 2427411Notes

Reaction equation

HRID 2427411 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][NH:4][C:3]1=[O:7].[BH3-]C#N.[Na+].[F:12][C:13]1[CH:14]=[C:15]([CH:26]=[CH:27][CH:28]=1)[CH2:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH:22]=O)=[CH:20][CH:19]=1.CS(O)(=O)=O>CO>[F:12][C:13]1[CH:14]=[C:15]([CH:26]=[CH:27][CH:28]=1)[CH2:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][NH:1][C@H:2]2[CH2:6][CH2:5][NH:4][C:3]2=[O:7])=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 8801194-[(3-Fluorophenyl)methoxy]benzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 12430456(3S)-3-aminopyrrolidin-2-one

Product 1

HCID 54532112(S)-3-[4-(3-fluorobenzyloxy) benzylamino]pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a 2M solution of (S)-3-aminopyrrolidin-2-one (1.47 g, 14.6 mmol), prepared as described in Example 5, in anhydrous methanol 2.0 g of 3 Å molecular sieves and 0.77 g NaBH3CN (12 mmol) were added; after 10 minutes, 3.4 g (14.8 mmol) of 4-(3-fluorobenzyloxy)benzaldeyde in 40 ml of anhydrous methanol were added. The reaction was carried out for 3 hours, then the mixture filtered, the solution was evaporated yielding a residue which was directly flash-chromatographed on silica gel (eluant: CHCl3:CH3OH:NH3 (30%) 97:3:0.3, v:v:v) to give a white solid (3.4 g; 74%). The free base thus obtained was treated with a stoichiometric amount of methanesulfonic acid to give the title compound m.p. 140.5-143.5° C.

Workup

  1. additionwere added
  2. waitThe reaction was carried out for 3 hours
  3. filtrationthe mixture filtered
  4. customthe solution was evaporated
  5. customyielding a residue which
  6. customwas directly flash-chromatographed on silica gel (eluant: CHCl3:CH3OH:NH3 (30%) 97:3:0.3, v:v:v)
  7. customto give a white solid (3.4 g; 74%)
  8. customThe free base thus obtained

Sources & evidence

ORD record
ord-6567a4387e2a4fad9329381a5d8a50e6
Source dataset
uspto-grants-2011_06
Patent number
US07968592B2

Reaction notes

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