4-[(1-Benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester → HCID 68891896, compound

HRID 1292849Notes

Reaction equation

HRID 1292849 reaction equation
[CH2:1]([Mg]Br)[CH3:2].[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([N:18]([C:20]([CH:22]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:23]2)=O)[CH3:19])[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([N:18]([C:20]2([CH:22]3[CH2:26][CH2:25][N:24]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:23]3)[CH2:2][CH2:1]2)[CH3:19])[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]

Participants

5

Reactant 2

HCID 694925584-[(1-Benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl esterHCID 178418443HCID 178418443, compound2×

Product 1

HCID 68891896HCID 68891896, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalyst2×HCID 8028TetrahydrofuranSolvent4×

Procedure

A stirred solution of ethylmagnesium bromide (3.0 M in ethyl ether, 2.1 mL, 6.3 mmol) in THF (17.0 mL) was cooled to −78° C. To this solution was added a solution of titanium (IV) isopropoxide (0.76 mL, 2.6 mmol) in THF (1.7 mL) dropwise with the temperature below −70° C. After stiring for three minutes, the solution of 4-[(1-benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 2.5 mmol) in THF (1.7 mL) was added. The resulting solution was slowly warmed to room temperature, heated at reflux for one hour and then cooled to 8° C. Ethylmagnesium bromide (3.0 M in ethyl ether, 1.8 mL, 5.4 mmol) was added followed by a solution of titanium (IV) isopropoxide (0.66 mL, 2.2 mmol) in THF (1.0 mL) rapidly. The reaction mixture was stirred at room temperature for one hour and partitioned between ethyl acetate and water. The separated organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative thin layer chromatography (60% ethyl acetate in hexane with 0.5% triethylamine) to give pale yellow oil (390 mg, 38%). ESI MS m/z 414.3 (M+H+).

Workup

  1. temperatureheated
  2. temperatureat reflux for one hour
  3. temperaturecooled to 8° C
  4. custompartitioned between ethyl acetate and water
  5. washThe separated organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative thin layer chromatography (60% ethyl acetate in hexane with 0.5% triethylamine)

Sources & evidence

ORD record
ord-310f4710747943d38d23474462f465ed
Source dataset
uspto-grants-2007_07
Patent number
US07238694B2

Reaction notes

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