Formaldehyde → (S)-5-biphenyl-4-ylmethyl-1-pyrrolidin-1-ylmethylpyrrolidin-2-one

HRID 1021044Notes

Reaction equation

HRID 1021044 reaction equation
[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[N:12]([C:13](=O)C(C)(C)C)C(=O)[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.[NH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1.[CH2:31]=[O:32]>C(O)C>[C:1]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([CH2:13][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[C:31](=[O:32])[CH2:10][CH2:9]2)=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 31268Pyrrolidine2×HCID 58160363(S)-5-[(biphenyl-4-yl)methyl]-1-(2,2-dimethylpropionyl)pyrrolidin-2-one

Product 1

HCID 59318460(S)-5-biphenyl-4-ylmethyl-1-pyrrolidin-1-ylmethylpyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 500 mg (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H), 329 μl pyrrolidine and 415 μl formaldehyde in 3.5 ml ethanol were heated at reflux for 3 h. A further quantity of 164 μl pyrrolidine and 148 μl formaldehyde were added and the mixture refluxed for about 24 h. The mixture was concentrated to dryness and purified by chromatography to obtain 533 mg of (S)-5-biphenyl-4-ylmethyl-1-pyrrolidin-1-ylmethylpyrrolidin-2-one (1-a, R1=methylpyrrolidin). 1H NMR (DMSO): 1.69 (4H, m, 2×NCH2CH2); 1.68-2.15 (4H, m, 3-CH2, 4-CH2); 2.50 (4H, 2×NCH2); 2.66 (1H, dd, 1-CHH); 3.12 (1H, dd, 1-CHH); 3.94 (1H, d, NCHHN); 4.21 (1H, d, NCHHN); 7.29 (2H, d, aromatic); 7.33 (1H, t, aromatic); 7.44 (2H, t, aromatic); 7.59 (2H, d, aromatic); 7.64 (2H, d, aromatic). m/z: 335 (MN+, 100%)

Workup

  1. temperaturewere heated
  2. temperatureat reflux for 3 h
  3. temperaturethe mixture refluxed for about 24 h
  4. concentrationThe mixture was concentrated to dryness
  5. custompurified by chromatography

Sources & evidence

ORD record
ord-13c77fa8988c49468abbc6a35ffa82e4
Source dataset
uspto-grants-2014_05
Patent number
US08716495B2

Reaction notes

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