Ethyl chloroformate → HCID 67490821, compound

HRID 1917327Notes

Reaction equation

HRID 1917327 reaction equation
Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[O:17]([CH2:35][C:36]1([C@H:39]2[CH2:43][C:42](=[O:44])[N:41]([C@H:45]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[CH3:46])[CH2:40]2)[CH2:38][CH2:37]1)[Si:18]([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O1CCCC1>[CH2:5]([O:4][C:2]([CH:43]1[C:42](=[O:44])[N:41]([C@H:45]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH3:46])[CH2:40][C@H:39]1[C:36]1([CH2:35][O:17][Si:18]([C:31]([CH3:32])([CH3:34])[CH3:33])([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:37][CH2:38]1)=[O:3])[CH3:6]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 2733832Lithium Hexamethyldisilazide2×HCID 67490801HCID 67490801, compound

Product 1

HCID 67490821HCID 67490821, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Ethyl chloroformate (0.059 mL, 0.617 mmol) and a solution of lithium hexamethyldisilazide in tetrahydrofuran (1.0 M, 0.57 mL, 0.570 mmol) were sequentially added dropwise to a solution of (3R)-3-[1-(tert-butyldiphenylsiloxymethyl)cyclopropan-1-yl]-5-oxo-1-[(1S)-1-phenylethyl]pyrrolidine (258 mg, 0.518 mmol) in tetrahydrofuran (2 mL) at 0° C. over two minutes. The mixture was stirred at 0° C. for 30 minutes and at room temperature for 30 minutes, and a solution of lithium hexamethyldisilazide in tetrahydrofuran (1.0 M, 0.57 mL, 0.570 mmol) was further added. The mixture was stirred at room temperature for 2.5 hours and then ice-cooled. The reaction was quenched with a 10% citric acid solution (20 mL). The resulting mixture was extracted with ethyl acetate (50 mL). The organic layer was washed with water (20 mL) and brine (20 mL) and then dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. Then, the resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9→1:4→1:2) to give 227 mg (77%) of the title compound as a colorless transparent gummy solid.

Workup

  1. stirringThe mixture was stirred at room temperature for 2.5 hours
  2. temperatureice-cooled
  3. customThe reaction was quenched with a 10% citric acid solution (20 mL)
  4. extractionThe resulting mixture was extracted with ethyl acetate (50 mL)
  5. washThe organic layer was washed with water (20 mL) and brine (20 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationAfter filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customThen, the resulting residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:9→1:4→1:2)

Sources & evidence

ORD record
ord-720086059ae549ee9857ae2d347cb142
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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