tert-Butyldimethylsilyl chloride → 2-(2-Benzyloxycarbonylamino-ethyl)-4-(tert-butyl-dimethyl-silanyloxy)-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester

HRID 1965155Notes

Reaction equation

HRID 1965155 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[O:13])[CH2:10][CH:9]1[CH2:14][CH2:15][NH:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1.[CH3:42][C:43]([Si:46](Cl)([CH3:48])[CH3:47])([CH3:45])[CH3:44]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([O:13][Si:46]([C:43]([CH3:45])([CH3:44])[CH3:42])([CH3:48])[CH3:47])=[CH:10][CH:9]1[CH2:14][CH2:15][NH:16][C:17]([O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:18])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 28928tert-Butyldimethylsilyl chlorideHCID 23700795NaHMDS tetrahydrofuranHCID 675061802-(2-Benzyloxycarbonylamino-ethyl)-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 675055862-(2-Benzyloxycarbonylamino-ethyl)-4-(tert-butyl-dimethyl-silanyloxy)-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl esterYield 83.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a pre-cooled (−78° C.) solution containing 6 (400 mg, 1.10 mmol) in THF (10 mL) was added 1M NaHMDS/THF (2.43 mL) in a dropwise fashion. After 45 min, a solution containing TBSCl (348 mg, 2.31 mmol) in THF (5 mL) was added to the heterogeneous reaction mixture. After 30 min, the homogeneous reaction mixture was quenched with saturated aqueous NH4Cl. The solution was diluted with EtOAc and the layers were separated. The organic phase was washed with brine then dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (4:1 hexanes/EtOAc) to afford 440 mg (83%) of 7 as a white foam. 1H NMR (CDCl3, 300 MHz), mixture of rotomers: δ7.26 (m, 5H), 5.87 (m, 0.25H), 5.70 (m, 0.25H), 5.48 (m, 0.5H), (app dd, J=16.4, 12.8 Hz, 2H), 4.92 (m, 0.3H), 4.55 (br s, 0.7H), 4.49 (m, 0.7H), 4.39 (m, 0.3H), 3.99 (m, 0.2H), 3.92 (m, 0.4H), 3.86 (br s, 0.4H), 3.76 (m, 1H), 3.28 (m, 0.5H), 3.13 (m, 0.5H), 3.03 (m, 0.5H), 2.92 (m, 0.5H), 1.78 (m, 1H), 1.64 (m, 1H), 1.38 (s, 9H), 0.85 (s, 9H), 0.11 (s, 6H) ppm. Mass spectrum, m/z [499.2] (M+Na)+.

Workup

  1. additionwas added to the heterogeneous reaction mixture
  2. waitAfter 30 min
  3. customthe homogeneous reaction mixture was quenched with saturated aqueous NH4Cl
  4. additionThe solution was diluted with EtOAc
  5. customthe layers were separated
  6. washThe organic phase was washed with brine
  7. dry with materialthen dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by flash silica gel chromatography (4:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-37ebdfffac9a4c5eae66ab3dfcf71b6f
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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