Chlorotrimethylsilane → 4-Allyl-2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester

HRID 639872Notes

Reaction equation

HRID 639872 reaction equation
[CH:1]([N-]C(C)C)([CH3:3])[CH3:2].[Li+].[CH3:9][O:10][C:11]([C:13]1([CH:20]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:17]([CH3:18])=[CH:16][C:15](=[O:19])[NH:14]1)=[O:12].Cl[Si](C)(C)C.C(Br)C=C>O1CCCC1>[CH3:9][O:10][C:11]([C:13]1([CH:20]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:29])[CH3:30])[CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:17](=[CH2:18])[CH:16]([CH2:3][CH:1]=[CH2:2])[C:15](=[O:19])[NH:14]1)=[O:12]

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 7841Allyl bromideHCID 2724682Lithium diisopropylamide2×HCID 685762772-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methyl-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester

Product 1

HCID 685760424-Allyl-2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl esterYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Lithium diisopropylamide solution (0.695 M solution in tetrahydrofuran, 5.66 ml, 3.93 mmol, 1.0 equiv) was added dropwise via syringe to a stirred solution of 2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methyl-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester (1.5 g, 3.93 mmol, 1.0 equiv) in tetrahydrofuran (45 ml) at −78° C. The reaction mixture was stirred at −78° C. for 30 min. Chlorotrimethylsilane (0.5 ml, 427 mg, 3.93 mmol, 1.0 equiv) was added and the resultant solution was stirred at −78° C. for 3 h. Another equiv of lithium diisopropylamide solution (0.695 M solution in tetrahydrofuran, 5.66 ml, 3.93 mmol, 1.0 equiv) was added dropwise at −78° C. The reaction mixture was stirred −78° C. for 30 min. Allyl bromide (0.68 ml, 0.951 g, 7.86 mmol, 2.0 equiv) was added dropwise via syringe at −78° C. The reaction mixture was stirred at −78° C. for 2 h. A buffer solution (pH=7, 100 ml) was added at −78° C. The mixture was extracted with ethyl acetate (50 ml×3). The combined organic layers were dried over sodium sulfate and the solids were filtered. The filtrate was concentrated. The residue was purified by flash column chromatography (10% ethyl acetate-hexanes initially, grading to 20% ethyl acetate-hexanes) to furnish 4-allyl-2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester (0.757 g, 46%) as a white solid.

Workup

  1. stirringThe reaction mixture was stirred −78° C. for 30 min
  2. stirringThe reaction mixture was stirred at −78° C. for 2 h
  3. extractionThe mixture was extracted with ethyl acetate (50 ml×3)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationthe solids were filtered
  6. concentrationThe filtrate was concentrated
  7. customThe residue was purified by flash column chromatography (10% ethyl acetate-hexanes initially

Sources & evidence

ORD record
ord-3100bec26f6940669344f38387d3526e
Source dataset
uspto-grants-2010_04
Patent number
US07691896B2

Reaction notes

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