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

HRID 1641658Notes

Reaction equation

HRID 1641658 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-e375c3a6b5a74807b80210fb4f7c545d
Source dataset
uspto-grants-2012_02
Patent number
US08115016B2

Reaction notes

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