Triethylamine → (S)-5-Biphenyl-4-ylmethyl-1-triethylsilanyl-pyrrolidin-2-one

HRID 882532Notes

Reaction equation

HRID 882532 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.C(N(CC)CC)C.[CH2:27]([Si:29]([CH2:33][CH3:34])([CH2:31][CH3:32])Cl)[CH3:28]>C1COCC1>[C:1]1([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[N:12]([Si:29]([CH2:33][CH3:34])([CH2:31][CH3:32])[CH2:27][CH3:28])[C:11](=[O:13])[CH2:10][CH2:9]2)=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 13819ChlorotriethylsilaneHCID 58160438(S)-5-[(Biphenyl-4-yl)methyl]pyrrolidin-2-one

Product 1

HCID 66739229(S)-5-Biphenyl-4-ylmethyl-1-triethylsilanyl-pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A dry flask is charged with 1.256 g (5 mmol) (S)-5-biphenyl-4-ylmethylpyrrolidin-2-one (1-a, R1=H) and 15 ml dry THF. To the resulting clear solution, 2.02 g (20 mmol) triethylamine is added followed by 904 mg (6 mmol) triethylchlorosilane (TES-Cl). The reaction mixture is stirred at room temperature for 4 h and then quenched on addition of 5 ml saturated NaHCO3 solution, 10 ml water and 10 ml isopropyl acetate. The layers are separated and the aqueous layer extracted with 10 ml isopropyl acetate. The combined organic layers are dried over MgSO4, filtered and evaporated. The resulting residue is purified by column chromatography (dichloromethane+1% v/v triethylamine) to give (S)-5-Biphenyl-4-ylmethyl-1-triethylsilanyl-pyrrolidin-2-one (1-a, R1=TES) as a yellow oil. NMR (300 MHz, DMSO-d6, /ppm): 7.63 (m, 4H); 7.55 (m, 2H); 7.32 (m, 3H); 3.80 (m, 1H); 2.85 (m, 1H), 2.70 (m, 1H), 2.10-1.70 (m, 4H), 1.02-0.80 (m, 15H). MS (ESI, m/e) 366 [M+H]+; 731 [2M+H]+. IR (solution in CH2Cl2, /cm−1): 3426; 3047; 2957; 1698; 1672; 1487; 1378; 1242; 1114; 1008.

Workup

  1. customquenched on addition of 5 ml saturated NaHCO3 solution, 10 ml water and 10 ml isopropyl acetate
  2. customThe layers are separated
  3. extractionthe aqueous layer extracted with 10 ml isopropyl acetate
  4. dry with materialThe combined organic layers are dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe resulting residue is purified by column chromatography (dichloromethane+1% v/v triethylamine)

Sources & evidence

ORD record
ord-e5d12526eb6e40a5b638c2e930e2024f
Source dataset
uspto-grants-2015_03
Patent number
US08993785B2

Reaction notes

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