Bromoacetonitrile → ((S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidin-1-yl)acetonitrile

HRID 882530Notes

Reaction equation

HRID 882530 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:14](C)(C)C)[C:11](=[O:19])[CH2:10][CH2:9]2)=[CH:3][CH:2]=1.C([Li])CCC.BrCC#[N:34]>C1COCC1.CCCCCC>[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[CH2:9][CH2:10][C:11](=[O:19])[N:12]2[CH2:13][C:14]#[N:34])=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 11534BromoacetonitrileHCID 58160363(S)-5-[(biphenyl-4-yl)methyl]-1-(2,2-dimethylpropionyl)pyrrolidin-2-oneHCID 178418339Butyllithium

Product 1

HCID 59318474((S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidin-1-yl)acetonitrile

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

1.5 g (5.97 mmol) (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1, R1═H) is dissolved in 15 ml dry THF and cooled to −78° C. After the addition of 4.13 ml butyl lithium in hexane (1.59 M) the yellow solution is stirred at −78° C. for 30 min. Subsequently, 475 l (855 mg, 7.16 mmol) bromoacetonitrile is added and the mixture is warmed up to room temperature overnight. The reaction is then quenched on addition of 10 ml saturated NH4Cl solution followed by the addition of 6 ml water and the mixture is extracted with 2×40 ml ethyl acetate. The combined organic layers are separated, dried over MgSO4, filtered and evaporated. The resulting residue is purified by column chromatography (dichloromethane:methanol=99:1) to give ((S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidin-1-yl)acetonitrile (1-a, R1=cyanomethyl) as off-white solid. NMR (400 MHz, DMSO-d6, /ppm): 7.65 (m, 4H); 7.47 (t, J=7.4, 2 H); 7.40 (m, 3H); 4.57 (d, J=17.7, 1H); 4.44 (d, J=17.7, 1H); 3.91 (m, 1H); 3.19 (dd, J=3.9, 13.8, 1H); 2.70 (dd, J=9.2, 13.8, 1H); 2.18 (m, 2H); 1.95 (m, 1H); 1.77 (m, 1H). MS (ESI, m/e) 291 [M+H]+. IR (solution in CH2Cl2, /cm−1): 3025; 2985; 2257; 1697; 1688; 1486; 1421; 1323; 1271; 1182; 760; 699.

Workup

  1. temperaturethe mixture is warmed up to room temperature overnight
  2. customThe reaction is then quenched on addition of 10 ml saturated NH4Cl solution
  3. additionfollowed by the addition of 6 ml water
  4. extractionthe mixture is extracted with 2×40 ml ethyl acetate
  5. customThe combined organic layers are separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe resulting residue is purified by column chromatography (dichloromethane:methanol=99:1)

Sources & evidence

ORD record
ord-b7ee4ff2454448f39a8f2fd8f0f441ad
Source dataset
uspto-grants-2015_03
Patent number
US08993785B2

Reaction notes

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