Triethylamine → (S)-1,3'-Bipyrrolidin-1'-YL(4-fluorophenyl)methanone

HRID 545302Notes

Reaction equation

HRID 545302 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.Cl.Cl.[N:13]1([C@H:18]2[CH2:22][CH2:21][NH:20][CH2:19]2)[CH2:17][CH2:16][CH2:15][CH2:14]1.C(N(CC)CC)C.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>CN(C=O)C>[N:13]1([C@H:18]2[CH2:22][CH2:21][N:20]([C:6]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)=[O:8])[CH2:19]2)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 99734-Fluorobenzoic AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 671716781-[(3S)-pyrrolidin-3-yl]pyrrolidine dihydrochloride

Product 1

HCID 59725829(S)-1,3'-Bipyrrolidin-1'-YL(4-fluorophenyl)methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-fluorobenzoic acid (3.5 g, 24.98 mmol) in DMF is treated with (S)-1,3′-bipyrrolidine dihydrochloride (10.65 g, 49.96 mmol), triethylamine (12.64 g, 124.90 mmol), 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (5.75 g, 28.98 mmol) and N-hydroxybenzotriazole (4.05 g, 29.98 mmol), stirred at room temperature for 16 h and concentrated in vacuo. The resultant residue is partioned between CH2Cl2 and H2O. The organic phase is separated, washed sequentially with saturated NaHCO3 and brine, dried over MgSO4 and concentrated. The concentrate is absorbed onto silica and purified by flash column chromatography (10% methanol in CH2Cl2) to give the title product, identified by NMR and mass spectral analyses.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe organic phase is separated
  3. washwashed sequentially with saturated NaHCO3 and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe concentrate is absorbed onto silica
  7. custompurified by flash column chromatography (10% methanol in CH2Cl2)

Sources & evidence

ORD record
ord-4a195029e5aa448ea5ee03f75c77d5fc
Source dataset
uspto-grants-2011_05
Patent number
US07935719B2

Reaction notes

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