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

HRID 1021054Notes

Reaction equation

HRID 1021054 reaction equation
Cl.C(O[C:5](=[O:23])[CH2:6][CH2:7][C@H:8]([NH2:22])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:12][CH:11]=1)C.[CH2:24]([N:26]([CH2:29][CH3:30])[CH2:27]C)[CH3:25]>C(OC(C)C)(=O)C>[C:13]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:12]=[CH:11][C:10]([CH2:9][C@H:8]2[N:22]([CH2:27][N:26]3[CH2:29][CH2:30][CH2:25][CH2:24]3)[C:5](=[O:23])[CH2:6][CH2:7]2)=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 66738936(S)-4-Amino-5-biphenyl-4-yl-pentanoic acid ethyl ester hydrochloride

Product 1

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

Reagents, catalysts & solvents 1

HCID 7915Isopropyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of (S)-4-Amino-5-biphenyl-4-yl-pentanoic acid ethyl ester hydrochloride [10-a, R5=Et] (86 g) in isopropyl acetate (1 L) is added triethylamine (43 g). The mixture is then stirred at about 55° C. for 1 h and then filtered. The filtrate is heated at reflux for 24 hours. To the mixture is added saturated ammonium chloride solution and the phases are separated. The organic layer is concentrated to dryness and crystallized from isopropyl acetate to yield (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one [Key Lactam (1-a, R1=H)]. Spectroscopic data agree with data provided above.

Workup

  1. filtrationfiltered
  2. temperatureThe filtrate is heated
  3. temperatureat reflux for 24 hours
  4. additionTo the mixture is added saturated ammonium chloride solution
  5. customthe phases are separated
  6. concentrationThe organic layer is concentrated to dryness
  7. customcrystallized from isopropyl acetate

Sources & evidence

ORD record
ord-ff9e68719ca946ed9d197843623cfc89
Source dataset
uspto-grants-2014_05
Patent number
US08716495B2

Reaction notes

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