Di-tert-butyl dicarbonate → (S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl ester

HRID 1641649Notes

Reaction equation

HRID 1641649 reaction equation
[C:1]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.[O:20](C(OC(C)(C)C)=O)[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:24]([O:23][C:21]([N:12]1[C@H:8]([CH2:7][C:4]2[CH:3]=[CH:2][C:1]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:6][CH:5]=2)[CH2:9][CH2:10][C:11]1=[O:13])=[O:20])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 2

HCID 90495Di-tert-butyl dicarbonate2×HCID 58160438(S)-5-[(Biphenyl-4-yl)methyl]pyrrolidin-2-one

Product 1

HCID 46193436(S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

8.6 g (S)-5-Biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H) (34.22 mmol) is dissolved in 135 ml methylene chloride. 4.2 g DMAP (34.22 mmol) is added. The mixture is further diluted with 10 ml methylene chloride. Then 14.9 g BOC2O (68.44 mmol) is added and further 10 ml methylene chloride is added. This reaction mixture is then stirred at reflux for 7.5 h. Then a further 3.7 g BOC2O is added. After a total reaction time of 24 h at reflux the solvent is evaporated completely. The evaporation residue is then filtered over 460 g of silica gel with an eluent of toluene:ethyl acetate 4:1. The product fractions are concentrated in vacuo to yield the crude product, which is recrystallised from methylene chloride/heptane fraction 1:6, to yield (S)-5-biphenyl-4-ylmethyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (1-a, R1=BOC).

Workup

  1. temperatureat reflux for 7.5 h
  2. temperatureAfter a total reaction time of 24 h at reflux the solvent
  3. customis evaporated completely
  4. filtrationThe evaporation residue is then filtered over 460 g of silica gel with an eluent of toluene:ethyl acetate 4:1
  5. concentrationThe product fractions are concentrated in vacuo
  6. customto yield the crude product, which
  7. customis recrystallised from methylene chloride/heptane fraction 1:6

Sources & evidence

ORD record
ord-4eebaba30d9e474b8617efafbcaa56ff
Source dataset
uspto-grants-2012_02
Patent number
US08115016B2

Reaction notes

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