Water → Benzyl 4-(pyrrolidin-3-yl)piperazine-1-carboxylate

HRID 1241417Notes

Reaction equation

HRID 1241417 reaction equation
O=[C:2]1[CH2:6][CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.[N:14]1([C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C([BH3-])#N.[Na+].O>C(O)C.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[NH:4]1[CH2:5][CH2:6][CH:2]([N:17]2[CH2:16][CH2:15][N:14]([C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[CH2:19][CH2:18]2)[CH2:3]1

Participants

7

Reactant 4

HCID 962WaterHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 643495Benzyl piperazine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 21934646Benzyl 4-(pyrrolidin-3-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of tert-butyl 3-oxopyrrolidine-1-carboxylate 45-1 (0.32 g, 1.73 mmol)), benzyl piperazine-1-carboxylate 45-2 (0.38 g, 1.73 mmol) and titanium tetraisopropoxide (0.61 g, 2.16 mmol) were stirred at 25° C. for 1 hour. Then the viscous solution was diluted with 2 mL of absolute ethanol and sodium cyanoborohydride (0.073 g, 1.16 mmol) was added. After stirring for 18 hours at 25° C., 1 mL of water was added and the solids filtered off. The filtrate was then dried under reduced pressure, redissolved in ethyl acetate, refiltered and evaporated. This material was purified on a silica column and then treated with trifluoroacetic acid to afford 45-3. 1H-NMR (CDCl3): 7.36(m, 5H); 5.13(s, 2H); 3.55(m, 4H); 3.26(m, 1H); 3.08(m, 1H); 2.80(m, 1H); 2.62(m, 1H); 2.49(m, 2H); 2.41(m, 2H); 2.08(m, 2H); 1.75(m, 1H).

Workup

  1. additionwas added
  2. stirringAfter stirring for 18 hours at 25° C.
  3. filtrationthe solids filtered off
  4. customThe filtrate was then dried under reduced pressure
  5. dissolutionredissolved in ethyl acetate
  6. customevaporated
  7. customThis material was purified on a silica column
  8. additiontreated with trifluoroacetic acid
  9. customto afford 45-3

Sources & evidence

ORD record
ord-2104e040ab524a79aca9d0e4e0c98e33
Source dataset
uspto-grants-2006_10
Patent number
US07115597B2

Reaction notes

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