(3R)-1-benzylpyrrolidin-3-amine → (R)-(1'-benzyl-3-bromo-[1,3']bipyrrolidinyl-2-one)

HRID 2306860Notes

Reaction equation

HRID 2306860 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:12][CH2:11][C@@H:10]([NH2:13])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:14][CH:15]([CH2:19][CH2:20]Br)[C:16](Br)=[O:17]>CC#N>[CH2:7]([N:8]1[CH2:12][CH2:11][CH:10]([N:13]2[CH2:20][CH2:19][C@@H:15]([Br:14])[C:16]2=[O:17])[CH2:9]1)[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 112898262,4-dibromobutanoyl Bromide

Product 1

HCID 23529702(R)-(1'-benzyl-3-bromo-[1,3']bipyrrolidinyl-2-one)Yield 63.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 5.0 g of (R)-1-(phenylmethyl)-3-pyrrolidinamine in 50.0 ml CH3CN was treated at rt with 2.72 g of Na3PO4. The resulting fine light yellow suspension was cooled to 0° C. and treated with a solution of 10.07 g of 2,4-dibromobutyrylbromide (prepared according to Marinelli, E. R.; Arunachalam, T.; Diamantidis, G.; Emswiler, J.; Fan, H.; Neubeck, R.; Pillai, K. M. R.; Wagler, T. R.; Chen, C.-K.; et al. Tetrahedron (1996), 52(34), 11177-11214) in 5.0 ml of CH3CN over 20 min. After 30 min the very fine suspension was filtered and concentrated to a volume of 30 ml, and then treated with 130.1 ml of 0.497 M NaOH solution at room temperature. The resultant turbid orange solution was stirred for 2 h, concentrated and the resultant aqueous phase extracted with three portions of 50 ml of TBME. The combined organic phases were washed with H2O until neutral, dried over MgSO4 and concentrated to give 5.79 g (63%) of (R)-(1′-benzyl-3-bromo-[1,3′]bipyrrolidinyl-2-one) as yellow waxy crystals.

Workup

  1. filtrationAfter 30 min the very fine suspension was filtered
  2. concentrationconcentrated to a volume of 30 ml
  3. additiontreated with 130.1 ml of 0.497 M NaOH solution at room temperature
  4. concentrationconcentrated
  5. extractionthe resultant aqueous phase extracted with three portions of 50 ml of TBME
  6. washThe combined organic phases were washed with H2O until neutral,
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-961118a02b6d4821b967a45b50d05205
Source dataset
uspto-grants-2004_12
Patent number
US06828442B2

Reaction notes

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