Water → 1-[1-(Diphenylmethyl)-3-azetidinyl]pyrrolidine

HRID 1063225Notes

Reaction equation

HRID 1063225 reaction equation
N1CCCC1.[CH2:6]([N:8]([CH2:11][CH3:12])[CH2:9][CH3:10])[CH3:7].[CH:13]([N:26]1[CH2:29][CH:28]([O:30][S:31]([CH3:34])(=[O:33])=[O:32])[CH2:27]1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>CN(C=O)C>[CH:13]([N:26]1[CH2:29][CH:28]([O:30][S:31]([CH3:34])(=[O:33])=[O:32])[CH2:27]1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1.[CH:13]([N:26]1[CH2:27][CH:6]([N:8]2[CH2:11][CH2:12][CH2:10][CH2:9]2)[CH2:7]1)([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 31268PyrrolidineHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonate

Product 2

HCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonateHCID 102663611-[1-(Diphenylmethyl)-3-azetidinyl]pyrrolidineYield 125.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Pyrrolidine (142 mg, 2 mmol) and triethylamine (100 mg, 1 mmol) were added to a solution of methanesulfonic acid 1-benzhydryl-azetidin-3-yl ester (317.4 mg, 1 mmol) in DMF (6 mL). (The methanesulfonic acid 1-benzhydryl-azetidin-3-yl ester was prepared as described in J. Org. Chem. 1991, 56, 6729-6730). The reaction mixture was heated at 70° C. overnight. After cooling to room temperature, the reaction mixture was treated with water. The aqueous layer was extracted with EtOAc (3×15 mL). The combined organic extracts were washed with brine and dried over sodium sulfate. The solvent was then removed under reduced pressure. Purification by flash chromatography on silica gel (CH2Cl2/MeOH 96:4) afforded the title compound as an oil (184 mg, 65%). MS: 293 (MH+); HPLC Rf: 5.95 min; HPLC purity: 92%.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted with EtOAc (3×15 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was then removed under reduced pressure
  6. customPurification by flash chromatography on silica gel (CH2Cl2/MeOH 96:4)

Sources & evidence

ORD record
ord-d1ea11ab06c043419ad7abb587b3956d
Source dataset
uspto-grants-2005_11
Patent number
US06964961B2

Reaction notes

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