4-Bromobenzoic acid → Pyrrolidine, 1-(4-bromobenzoyl)-2-(1-pyrrolidinylmethyl)-, (2S)-

HRID 1923474Notes

Reaction equation

HRID 1923474 reaction equation
O=C1CCC(=O)N1O[C:9](=[O:17])[C:10]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=1.BrC1C=CC(C(O)=O)=CC=1.ONC(=O)CCC(N)=O.[NH:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[CH2:42][N:43]1[CH2:47][CH2:46][CH2:45][CH2:44]1>O1CCCC1>[Br:16][C:13]1[CH:12]=[CH:11][C:10]([C:9]([N:37]2[CH2:41][CH2:40][CH2:39][C@H:38]2[CH2:42][N:43]2[CH2:47][CH2:46][CH2:45][CH2:44]2)=[O:17])=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 114644-Bromobenzoic acidHCID 853152(S)-(+)-1-(2-Pyrrolidinylmethyl)pyrrolidineHCID 138964302,5-Dioxopyrrolidin-1-yl 4-bromobenzoateHCID 18381240N-hydroxysuccinamide

Product 1

HCID 11965129Pyrrolidine, 1-(4-bromobenzoyl)-2-(1-pyrrolidinylmethyl)-, (2S)-Yield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 4-bromobenzoic acid-2,5-dioxo-pyrrolidin-1-yl ester (3.5 g, 11.7 mmol), [which can be prepared from 4-bromobenzoic acid and N-hydroxy succinamide by the method of C. Mitsos, Chem Pharm Bull 48(2), 211-214 (2000), or purchased from Ambinter, CAS# 80586-82-9], in tetrahydrofuran (0.15 M), add (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine and heat to reflux for 4 h. After this time, remove the heat and wash the reaction with water while extracting with 10% isopropanol/dichloromethane. Dry the organic portion with sodium sulfate, filter and concentrate in vacuo. Purify the resulting residue on a silica column eluting with 2 M ammonia in methanol and dichloromethane to give (4-bromo-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-yl)methanone (93% yield with 80% purity). MS (m/e): 337.1 (M+1).

Workup

  1. temperatureheat
  2. temperatureto reflux for 4 h
  3. customAfter this time, remove the
  4. temperatureheat
  5. washwash
  6. customthe reaction with water
  7. extractionwhile extracting with 10% isopropanol/dichloromethane
  8. dry with materialDry the organic portion with sodium sulfate
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customPurify the resulting residue on a silica column
  12. washeluting with 2 M ammonia in methanol and dichloromethane

Sources & evidence

ORD record
ord-3bf9d77cf5db45c5ac23afc49af7cc3c
Source dataset
uspto-grants-2012_05
Patent number
US08178528B2

Reaction notes

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