Cyclohexanecarboxaldehyde → 2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methyl-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester

HRID 639868Notes

Reaction equation

HRID 639868 reaction equation
[Si:1]([O:8]S(C(F)(F)F)(=O)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:16][O:17][C:18]([C:20]1[NH:21][C:22]([O:26][Si](C(C)(C)C)(C)C)=[CH:23][C:24]=1[CH3:25])=[O:19].[CH:34]1([CH:40]=O)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>ClCCl>[CH3:16][O:17][C:18]([C:20]1([CH:40]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[C:24]([CH3:25])=[CH:23][C:22](=[O:26])[NH:21]1)=[O:19]

Participants

5

Reactant 3

HCID 16275CyclohexanecarboxaldehydeHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 575874385-(Tert-butyl-dimethyl-silanyloxy)-3-methyl-1h-pyrrole-2-carboxylic acid methyl ester

Product 1

HCID 685762772-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methyl-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl esterYield 85.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyldimethylsilyltrifluoromethanesulfonate (2.40 ml, 2.75 g, 10.4 mmol, 2.0 equiv) was added dropwise over 8 min to a stirring solution of 5-(tert-butyl-dimethyl-silanyloxy)-3-methyl-1H-pyrrole-2-carboxylic acid methyl ester (1.4 g, 5.2 mmol, 1.0 equiv) and cyclohexanecarbaldehyde (0.94 ml, 0.87 g, 7.8 mmol, 1.5 equiv) in dichloromethane (100 ml) at −78° C. The resultant solution was stirred at −78° C. for 2 h, then pH=7 buffer solution (50 ml) was added. The organic layer was washed with brine solution (50 ml), and dried over sodium sulfate. The solids were filtered and the filtrate was concentrated. The residue obtained was purified by flash column chromatography (5% ethyl acetate-dichloromethane initially, grading to 8% ethyl acetate-dichloromethane, then to 10% ethyl acetate-dichloromethane) to give 2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-3-methyl-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid methyl ester (1.69 g, 85%) as a colorless oil.

Workup

  1. washThe organic layer was washed with brine solution (50 ml)
  2. dry with materialdried over sodium sulfate
  3. filtrationThe solids were filtered
  4. concentrationthe filtrate was concentrated
  5. customThe residue obtained
  6. customwas purified by flash column chromatography (5% ethyl acetate-dichloromethane initially

Sources & evidence

ORD record
ord-74a4be04148542ff9fc120b412960eb2
Source dataset
uspto-grants-2010_04
Patent number
US07691896B2

Reaction notes

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